这项工作得到了吉林省科学技术厅（YDZJ202201ZYTS181）的支持。

该动物程序已获得长春中医药大学伦理委员会批准（备案号：2021214）。将无特定病原体的C57BL / 6J小鼠（8-10周，体重18-22g），雄性和雌性，饲养在22°C和65%相对湿度的独立通风笼中。小鼠在适应性喂养7天后开始实验，在此期间它们可以自由获得水和饮食。
1.药物制备
<ol><li>LJZD的制备 注：所用中药购自长春中医药大学附属医院，经鉴定为正品中药（见 表1）。<ol><li>将当神（12g）、白术（12g）、赣草（6g）、陈皮（12g）、姜板峡（9g）放入专用陶瓷锅中（见 材料表）。加入1000mL蒸馏水，在室温下浸泡1小时（见 图1A）。</li>
		<li>粉末12g涪凌用研磨机研磨成细粉，并在室温下在另一个容器中的300mL蒸馏水中浸泡1小时。</li>
		<li>将上述中药混合在专用陶瓷锅中。将混合物煮沸，然后保持中火，直到只剩下 300 mL 汤剂。使用医用纱布进行过滤，并将滤液保存在室温下。</li>
		<li>加入 1000 mL 蒸馏水，再次重复上述煎煮操作。再次用医用纱布过滤。将滤液混合并煮沸至仅剩 150 mL。</li>
		<li>将浓缩液体以10,000× g 离心5分钟，并将获得的上清液进一步浓缩至30mL。将最终浓缩物转移到培养皿中，并使用电动烘箱干燥，直到只有溶质保留为粉末。</li>
		<li>称取上述固体，溶于无菌蒸馏水中，得到每0.2mL（114.16mg/mL）含22.85mg药物的溶液，即为小鼠日用量。</li>
	</ol></li>
	<li>5-氨基水杨酸的制备 注：5-氨基水杨酸（5-ASA;见 材料表）对UC-CRC有良好的预防作用，在本研究中被用作阳性药物23。<ol><li>将 64 mg 5-ASA 粉末溶解在 200 mL 无菌蒸馏水中，得到 1.82 mg/mL 5-ASA 溶液。单只小鼠的日剂量为0.2mL。</li>
	</ol></li>
	<li>AOM注射液的制备<ol><li>将2.5mL无菌蒸馏水加入25mg AOM粉末中（见 材料表），并通过涡旋混合器（见 材料表）混合制成10mg / mL AOM储备溶液，储存在-20°C直至使用。</li>
		<li>通过用无菌蒸馏水以 10：1 （1 mg/mL） 稀释 AOM 储备溶液来制备 AOM 注射液。</li>
	</ol></li>
</ol>2. UC-CRC模型的建立
注：实验分为4组：对照组、模型组、LJZD组和5-ASA组，每组10只小鼠。除对照组外，其他组均接受AOM和DSS治疗。
<ol><li>腹腔注射AOM注射液 注意：适应性喂养7天后，通过腹膜内注射给予小鼠AOM注射液（1mg / mL）（见 图1B）。<ol><li>保持鼠标的腹部朝上，头部略微向下。握住背部皮肤以收紧腹部皮肤，并用 1 mL 注射器刺穿中腹部线上两条大腿根线交叉处约 1 厘米处的皮肤（见 材料表）。</li>
		<li>将 1 mL 注射器针头推到皮肤下 3-5 mm 的距离，使其与腹部中线平行，然后将针头以 45° 插入腹腔 0.3-0.5 mm。</li>
		<li>尖端穿过腹部肌肉后，操作者会感觉到阻力突然丧失。随后，向外和向后拉动注射器，观察是否发生液体渗漏。如果没有，将AOM注射液以0.1mL / 10g缓慢推入小鼠体内。</li>
	</ol></li>
	<li>2%DSS溶液的循环刺激 注意：每只AOM诱导的小鼠在第3、6和9周给予500mL DSS溶液，在此期间小鼠自由饮水。<ol><li>通过向 10 g DSS 中加入 500 mL 无菌蒸馏水来制备 2% DSS 溶液（参见 材料表）。与涡旋混合器混合，并在4°C下储存直至使用。</li>
		<li>在AOM诱导后的第3周，第6周和第9周，每个AOM诱导的小鼠自由饮用500mL 2%DSS溶液7天。</li>
	</ol></li>
</ol>3.药物治疗
注意：成年人每天需要 63 克 LJZD。根据实验小鼠与人药物剂量的换算公式，小鼠的当量实验剂量（mg/kg）=人剂量（mg/kg）/体重（60kg）×9.1，小鼠的日剂量约为9.6g/kg。
<ol><li>分别在第 7 周和第 15 周通过胃管饲法用 0.1 mL/10 g 制备的 LJZD 和 5-ASA 溶液治疗 LJZD 和 5-ASA 组。<ol><li>对于小鼠的胃内给药，请执行以下程序。左手握住鼠标，右手握住胃灌注装置。将注射器针头插入口腔，然后将其滑下小鼠咽部的后壁。当小鼠吞咽时，沿着咽部滑动并继续前进。当有抵抗感，注射器可以推入咽部时，拔出针头并完成注射。</li>
	</ol></li>
	<li>用相同量的生理盐水处理对照组和模型组（参见 材料表）。</li>
	<li>在给药期间每天一次用适当的药物治疗每组小鼠。</li>
</ol>4. UC-CRC模型的评价及LJZD的疗效
<ol><li>疾病活动指数评分 注：根据 表2，通过结合小鼠的体重减轻，粪便粘度和粪便出血来评估疾病活动指数（DAI）评分。<ol><li>从适应性喂养开始到药物治疗结束，每天记录小鼠的体重。</li>
		<li>仔细观察每只实验小鼠的粪便稠度，并将排便记录为三种情况之一：正常、稀便和水样腹泻。</li>
		<li>将实验动物的粪便出血记录为三种情况之一：无出血、少量出血、便血可见。</li>
	</ol></li>
	<li>检测血清中IL-6水平<ol><li>用LJZD或5-ASA治疗小鼠9周。用左手抓住小鼠的颈部皮肤，轻轻按压实验台，采取侧卧位，固定小鼠。用剪刀剪掉老鼠的胡须。用剪刀小心地剪掉小鼠的胡须（见 材料表），以防止血液污染。 注意：不能自由摆动的老鼠被认为是正确固定的。如果没有发生这种情况，则应固定鼠标。</li>
		<li>通过吸入2%异氟烷麻醉小鼠。用乙醇对眼球周围的皮肤进行消毒（见 材料表）。轻轻按压侧面的眼部皮肤，使眼球充血突出。</li>
		<li>用肘部镊子夹住眼球，准确快速地取出眼球。让血液滴入离心管中（见 材料表）。在此过程中，点击鼠标的心脏以加快采血速度。</li>
		<li>将收集的血液在室温下保持30分钟，并以3,500× g 离心10分钟。收集上清液并根据IL-6含量检测试剂盒说明检测IL-6水平（参见 材料表）。</li>
	</ol></li>
	<li>分离结直肠组织<ol><li>根据动物伦理，通过吸入5%过量的异氟醚和宫颈脱位（见 材料表）对小鼠进行血液采样后实施安乐死。</li>
		<li>将小鼠保持在低温解剖环境中。将小鼠固定在仰卧位。用剪刀剪下腹部毛发，并用乙醇消毒。</li>
		<li>用眼睑镊夹住两个大腿根部和腹部中线之间的交点（见 材料表）。用剪刀剪一个约1-1.5厘米的横切口。</li>
		<li>从横切口的中点沿腹部正中线向剑突夹一个纵向切口。</li>
		<li>沿肛门方向取出结直肠周围组织，将结直肠与周围组织分开。注意不要损坏结直肠。</li>
		<li>将腹部皮肤向两侧推，使结直肠完全暴露。用眼睑镊子从腹腔中取出结直肠，并切断从肛门到盲肠的部分（不包括）;总长度约为10厘米。将获得的结直肠组织储存在4°C的盐水中。</li>
	</ol></li>
	<li>直肠长度和重量的评估<ol><li>用5mL针头在4°C下提取生理盐水（参见 材料表）以冲洗结直肠内部。然后，将结直肠放在吸水纸上以吸收组织的水分。</li>
		<li>称量结直肠组织，然后将它们放在 A4 纸上测量其长度。</li>
	</ol></li>
	<li>测量结直肠肿瘤的数量<ol><li>纵向切开结直肠以使其完全展开，并观察结直肠中肿瘤的数量和大小。</li>
	</ol></li>
	<li>结直肠的病理分析<ol><li>将结直肠固定在4%多聚甲醛中24小时。将固定的直肠组织嵌入熔化的石蜡中，并通过组织冷冻切片机以5μm的厚度连续切片。</li>
		<li>根据Hou等人24的程序，在二甲苯中对切片进行脱蜡，然后用连续浓度的乙醇脱水。用苏木精溶液染色5分钟后，用纯净水冲洗切片。之后，用0.5%曙红溶液染色1分钟（见 材料表）。</li>
		<li>再次进行梯度脱水和二甲苯透明处理。密封切片并在光学显微镜下观察它们（见 材料表）和照片，如Xie等人25所述。</li>
	</ol></li>
	<li>结直肠的免疫组织化学分析<ol><li>按上述方法对切片进行脱蜡和脱水。用高压热修复技术修复切片中的抗原，如Gok等人26所述。</li>
		<li>将切片在室温下浸泡在内源性过氧化物酶阻滞剂中15分钟。用山羊血清密封切片（见 材料表）。</li>
		<li>将一抗ZO-1（1：1000），Occludin（1：1000）和KI67（1：500;参见 材料表）加入切片中，并在4°C下孵育过夜。 用PBS缓冲液冲洗切片（见 材料表），加入通用二抗（1：5000;见 材料表），并在37°C孵育30分钟。</li>
		<li>将 DAB 解决方案（请参阅 材料表）添加到显色部分。用苏木精溶液对切片进行复染。</li>
		<li>再次对切片进行脱水、透明和密封。通过光学显微镜观察蛋白质的表达。</li>
	</ol></li>
</ol>

六君子汤：预防 UC-CRC 的有效治疗方法

作者没有什么可透露的。

结直肠癌是全球最常见的癌症之一，每年约有 1,148,000 例新发病例和超过 576,000 例死亡。结直肠癌根据病因不同可分为3种类型，包括遗传性、散发性和UC-CRC31。UC等炎症性肠病患者的CRC发病率明显高于一般人群。UC 通过炎症-癌症通路刺激 CRC 的发展，这与典型的腺瘤-腺癌通路不同 6。目前UC-CRC的病因不明，主要由长期复发性慢性炎症引起，死亡率高达60%32,33。UC-CRC目前尚无有效的治疗方法，UC-CRC是近年来研究的热点。了解UC-CRC的分子机制对于UC-CRC的早期检测和精确治疗至关重要。
目前，构建UC-CRC动物模型的方法很多，形成机制也不同。IL-10 或 Muc2/4 基因敲除导致上皮屏障缺陷，可诱导小鼠自发性结肠炎，因此常用于基于与 UC 相关的遗传缺陷构建动物 CRC 模型34、35、36。然而，基因敲除诱导的UC-CRC动物模型无法模拟该病的完整发病机制，且其操作方法复杂，实验成本高，局限性明显。化学诱导是构建UC-CRC动物模型的经典和常用方法37,38。DSS、AOM和二甲基肼都是构建UC-CRC的常用化学诱导剂。然而，单独使用这些化学试剂建立动物模型需要很长时间，并且成功率很低39。研究表明，AOM和DSS联合诱导的UC-CRC发生率几乎可以达到100%40。与其他方法相比，AOM/DSS联合使用具有操作简单、可控性强、周期短、复制率高等优点，在病理学和分子机制方面能更好地模拟人UC-CRC 40,41,42。虽然采用AOM/DSS循环刺激构建UC-CRC模型具有诸多优点，但也存在建模时间长、建模试剂昂贵、仍不能完全模拟人UC-CRC发病机制的缺点。
为了寻找UC-CRC的潜在治疗靶点，我们使用化学致癌物AOM与DSS诱导的小鼠相结合，建立了UC-CRC模型。在这项研究中，暴露于AOM和DSS周期刺激的小鼠表现出不同程度的UC-CRC相关症状。与对照组相比，模型组DAI评分显著升高，表现为体重减轻、血便、稀便、水样腹泻。而 LJZD 显着降低了 DAI 评分。结直肠长度缩短是 UC-CRC43,44 炎症反应的重要标志物。本研究显示，模型小鼠结直肠长度明显短于对照组，LJZD可改善结直肠缩短。结直肠粘膜发生慢性炎症，逐渐演变为结直肠组织的非典型增生，最终导致癌症45。本研究显示，模型组小鼠结直肠组织肿瘤数量较对照组显著增加，结直肠组织重量也相应增加。LJZD治疗后，肿瘤数量明显减少，结直肠重量下降。研究表明，LJZD对UC诱导的CRC的形成具有显著的抑制作用。既往研究发现，LJZD可以缓解炎症，降低体内TNF-α、IL-6和IL-1β的表达水平16,28,46。本研究显示，模型组小鼠血清IL-6水平升高，LJZD治疗后血清IL-6的产生明显抑制。
显微镜观察显示，AOM/DSS治疗小鼠直肠组织炎性浸润，黏膜屏障破坏，黏液分泌减少，杯状细胞不规则或消失，肠隐窝变形或萎缩，腺体结构明显紊乱。LJZD治疗后，结直肠组织杯状细胞形态正常，凹陷和腺体结构规则，黏膜屏障损伤改善。上皮紧密连接（TJ）是维持细胞完整性和通透性不可或缺的机械屏障，主要包括ZO-1和Occludin29。据报道，TJ蛋白（如ZO-1）在UC-CRC患者的结直肠组织中的表达显着降低47,48。本研究表明，UC-CRC小鼠结直肠黏膜组织结构被破坏，组织中ZO-1和Occludin的表达降低，而LJZD可以逆转这种下降，表明LJZD可能通过增加ZO-1和Occludin的表达来保护结直肠黏膜屏障的完整性。核相关抗原 （KI67） 是细胞周期调节的重要组成部分，被广泛用作肿瘤细胞增殖活性的指标30,49。在这项研究中，与对照组相比，模型组的 KI67 蛋白表达增加，表明结直肠组织中肿瘤细胞显着增殖。LJZD处理后，KI67蛋白表达降低，表明LJZD对UC-CRC有较好的作用。
综上所述，AOM腹腔注射和DSS循环刺激可在短时间内有效建立UC-CRC模型，在组织病理学和形成分子机制上与人UC-CRC相似。LJZD作为一种经典处方，可降低DAI评分、结直肠组织重量和炎症因子水平，有效抑制结直肠长度缩短，在UC-CRC小鼠UC分期中发挥作用。同时可增加TJ蛋白的表达，显著改善结直肠组织的病理损伤，降低KI67蛋白的表达，显著降低组织肿瘤的发生率，抑制UC向CRC的转化过程。本研究为UC-CRC的治疗提供了新的思路。

结直肠癌（CRC）是一种常见的胃肠道恶性肿瘤，是全球第三大常见恶性肿瘤，也是全球第二大常见死因，占全球癌症发病率的10%，占癌症相关死亡总数的9.4%1,2。遗传因素、慢性炎症、高脂肪饮食、糖尿病和肠道菌群异常是 CRC 3,4 的危险因素。其中，炎症性肠病，尤其是溃疡性结肠炎（UC），是CRC 5,6的明显危险因素。UC相关结直肠癌（UC-CRC）是基于结直肠慢性炎症的炎症、非典型增生和癌症的过渡过程，与CRC 7,8的典型腺瘤-腺癌发展模型不同。与一般人群相比，炎症性肠病患者患CRC的风险大约高出10-40倍9。
目前，手术仍然是 CRC 的标准治疗方法，并且根据肿瘤的位置和阶段，放射治疗、全身药物治疗或两者的组合是可能的10。虽然这些传统的治疗方式已经取得了很大的进展，但由于结直肠癌的异质性和复发率高，预后较差，治疗效果不理想11,12。因此，早期发现、早期诊断、综合治疗是提高结直肠癌患者生存率的关键，关注结直肠癌向结直肠癌的转化尤为重要。多年来，中医药因其副作用有限、疗效显著而在治疗UC-CRC或慢性胃炎方面备受关注。历代著名中医在辩证法的基础上，创作了大量的经典药方，如黄旗建中汤13、四君子汤14、思神丸15等。
流君子汤（LJZD）起源于明代编纂的易雪正传著作，是中医16中的经典处方。如表1所示，LJZD由六种传统草本植物组成，包括党参（Codonopsis pilosula，Franch.）南夫。（当神）、茯苓（Schw.）、狼（涪陵）、苍术（Atractylodes macrocephala Koidz）。（白术）， Glycyrrhiza uralensis Fisch.（Gancao）、柑橘（Citrus reticulata Blanco）和Pinellia ternata（Thunb.）蒲公英（半夏），具有补气健脾、干湿化痰的作用。在现代临床实践中，常用于治疗慢性胃炎、胃溃疡和十二指肠溃疡。现代药理学研究表明，LJZD和改良的LJZD在UC和消化道癌的辅助治疗中具有较高的应用价值17,18,19。
目前UC-CRC小鼠模型的构建方法很多，但偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导的小鼠模型是应用最广泛的UC-CRC模型;临床症状、形态学和病理学观察证明，该模型与人类UC-CRC20,21非常相似。其基本原理是先用化学致癌物AOM诱导致癌作用，然后连续将小鼠暴露在DSS的炎症刺激环境中，模拟肠粘膜上皮的连续损伤和修复，从而构建UC-CRC小鼠模型22。本研究的目的是在短期内通过腹腔注射AOM和DSS的循环刺激建立UC-CRC的小鼠模型，并评价该药物和LJZD对UC-CRC的分子机制，以期为UC-CRC的治疗提供科学依据。

<table><tbody><tr><td>Azoxymethane</td><td>Sigma</td><td>A5486</td><td></td></tr><tr><td>5-amino salicylic acid</td><td>Kuihua Pharmaceuticals Group Jiamusi Luling Pharmaceutical Co., Ltd</td><td>3819413</td><td></td></tr><tr><td>C57BL/6J mice</td><td>Liaoning Changsheng Biotechnology Co., Ltd</td><td>NO 210726210100853716</td><td></td></tr><tr><td>Cover slip</td><td>Jiangsu Shitai Experimental Equipment Co., Ltd</td><td>10212432C</td><td></td></tr><tr><td>DAB color development kit</td><td>Jiangsu Shitai Experimental Equipment Co., Ltd</td><td>2005289</td><td></td></tr><tr><td>Dewatering machine&amp;nbsp;</td><td>Wuhan Junjie Electronics Co., Ltd</td><td>JJ-12J</td><td></td></tr><tr><td>Dextran sulfate sodium</td><td>Dalian Meilun Biotechnology Co., Ltd</td><td>MB5535</td><td></td></tr><tr><td>Embedding machine</td><td>Wuhan Junjie Electronics Co., Ltd</td><td>JB-P5</td><td></td></tr><tr><td>Hematoxylin-eosin dye</td><td>Wuhan Hundred Degree Biotechnology Co., Ltd</td><td>B1000</td><td></td></tr><tr><td>IL-6</td><td>Jiangsu Meimian Industrial Co., Ltd</td><td>MM-0163M2</td><td></td></tr><tr><td>Isoflurane</td><td>RWD Life Science Co., Ltd</td><td>R510-22-10</td><td></td></tr><tr><td>KI67 primary antibody</td><td>Google Biotechnology Inc</td><td>GB121141</td><td></td></tr><tr><td>Neutral gum</td><td>Wuhan Hundred Degree Biotechnology Co., Ltd</td><td>10004160</td><td></td></tr><tr><td>Object slide</td><td>Jiangsu Shitai Experimental Equipment Co., Ltd</td><td>10212432A</td><td></td></tr><tr><td>Occludin primary antibody</td><td>Affnity</td><td>DF7504</td><td></td></tr><tr><td>Orthostatic optical microscope</td><td>Nikon</td><td>Nikon Eclipse CI</td><td></td></tr><tr><td>Pathological microtome</td><td>Shanghai Leica Instrument Co., Ltd</td><td>RM2016</td><td></td></tr><tr><td>ZO-1 primary antibody</td><td>Abcam</td><td>ab221547</td><td></td></tr></tbody></table>

establishment of coloproctitis cancer model in mice and evaluation of therapeutic effect of chinese medicine

结直肠癌 （CRC） 是一种常见的消化系统恶性肿瘤，已成为全球第三大常见恶性肿瘤和恶性肿瘤相关死亡的第二大原因。溃疡性结肠直肠炎 （UC） 是一种癌前病变，UC 相关 CRC （UC-CRC） 是 CRC 最常见的亚型。因此，合理的UC-CRC模型是新药研发的基石和保障。中医药（TCM）因其良好的疗效而被广泛用于治疗UC-CRC。柳君子汤（LJZD）作为中医的经典补药方，已被广泛用于治疗UC-CRC。本研究结合偶氮甲烷和硫酸葡聚糖钠建立UC-CRC模型，并给予LJZD。数据证实，LJZD可利用小鼠体重、结直肠长度、病理炎症因子、结直肠屏障功能、癌症标志物等手段有效抑制UC-CRC的癌症转化。该协议提供了一个评估中医预防和治疗UC-CRC疗效的系统。

LJZD的汤剂按表1中药物的组成比例和图1A中的中药的汤剂方法制备。根据图1B所示的时间点，小鼠在第7天腹膜内注射1 mg/mL AOM，在第3、6、9周自由饮用含有2%DSS的饮用水。UC-CRC小鼠模型在第15周成功建立。同时，从第7周到第15周，通过强饲法对小鼠进行LJZD处理。数据显示，与对照组相比，UC-CRC模型组体重减轻显著，LJZD治疗缓解了体重减轻（图2A，P<0.01）。在试验结束时，与UC-CRC模型组相比，LJZD治疗改善了DAI评分（图2B）。与对照组相比，UC-CRC模型组的结直肠长度较短，LJZD治疗增加了结直肠长度（图2C，D，P<0.01）。结直肠重量与体重的比率反映了小鼠CRC的发展，较高的比率表明急性肿瘤发展27。与对照组相比，模型组结直肠器官指数显著升高，LJZD治疗大大降低了结直肠器官指数（图2E，P<0.05）。此外，LJZD治疗还抑制了结直肠肿瘤的形成（图2F，P<0.01）和血清促炎因子IL-6的水平28（图2G，P<0.05）。
病理结果证实，与对照组相比，UC-CRC模型组小鼠结直肠肿瘤较大，已形成腺癌，而LJZD治疗减小了肿瘤的大小和分级（图3）。免疫组织化学数据表明，LJZD治疗增强了UC-CRC模型小鼠的结直肠屏障功能，如ZO-1和Occludin29 蛋白表达升高所示（图4）。同时，LJZD治疗抑制了癌症标志物KI6730 的蛋白表达水平（图4）。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/66045/66045fig01.jpg"> 图1：LJZD的制备和结肠直肠炎癌小鼠模型的建立。A）将当神（12 g）、白术（12 g）、赣草（6 g）、陈皮（12 g）和生姜加工的半夏（9 g）的混合物在室温下浸泡在1000 mL蒸馏水中1 h。将12 g涪陵粉末在室温下浸泡在300 mL蒸馏水中1 h。将上述六种草药的混合物在100°C下煎煮40分钟。 （B）第7天，C57BL/6J小鼠腹腔注射1 mg/mL AOM。小鼠在第3周、第6周和第9周随意给予含有2%DSS的水。从7到15周，通过管饲法给予小鼠LJZD。缩写：AOM，偶氮甲烷;DAI， 疾病活动指数;DSS，葡聚糖硫酸钠;LJZD， 柳君子汤;w， 周。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66045/66045fig01large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/66045/66045fig02.jpg"> 图2：UC-CRC模型的评估和LJZD的疗效。（A） LJZD改善了UC-CRC模型小鼠的体重。 （B） LJZD 缓解了 UC-CRC 模型小鼠的 DAI 评分。 （C、D） LJZD增加了UC-CRC模型小鼠的结直肠长度。 （E） LJZD降低了UC-CRC模型小鼠结直肠的器官指数。 （F） LJZD抑制结肠直肠炎癌模型小鼠的结直肠肿瘤发生。 （G） LJZD抑制UC-CRC模型小鼠血清IL-6水平。 #与对照组相比，P<0.05和 ##P<0.01; *与模型组相比，P < 0.05 和 **P< 0.01。数据表示为均值±标准差 （n=10），并通过单因素方差分析 （ANOVA） 进行分析，然后进行 Tukey 检验。P < 0.05 表示差异有统计学意义。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66045/66045fig02large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/66045/66045fig03.jpg"> 图3：苏木精-伊红染色评价小鼠结直肠组织的病理特征。 对照组无病理损伤。UC-CRC模型组肿瘤组织较大，已形成腺癌和高级别肿瘤，而LJZD治疗组肿瘤组织减少，伴有少量局部腺瘤和低级别肿瘤。黑色箭头代表癌前发育不良肿瘤腺体。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66045/66045fig03large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/66045/66045fig04.jpg"> 图4：LJZD对UC-CRC模型小鼠结直肠屏障功能和癌症标志物的影响。（A） ZO-1、Occludin 和 KI67 的免疫组织化学图像。 （B） ZO-1、Occludin 和 KI67 蛋白表达的统计结果。LJZD治疗增加了UC-CRC模型小鼠中结直肠屏障功能蛋白ZO-1和Occludin的表达，同时降低了癌症标志物KI67的水平。 ## 与对照组相比，P<0.01; ** 与模型组相比，P<0.01。数据表示为均值±标准差 （n=10），并通过单因素方差分析 （ANOVA） 进行分析，然后进行 Tukey 检验。P < 0.05 表示差异有统计学意义。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66045/66045fig04large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody><tr><td>组件</td>
			<td>拼音</td>
			<td>重量 （g）</td>
		</tr><tr><td>党参基</td>
			<td>当神</td>
			<td>12</td>
		</tr><tr><td>茯苓</td>
			<td>涪陵</td>
			<td>12</td>
		</tr><tr><td>Atractylodis Macrocephalae Rhizoma</td>
			<td>白术</td>
			<td>12</td>
		</tr><tr><td>甘草</td>
			<td>赣草</td>
			<td>6</td>
		</tr><tr><td>干橙皮</td>
			<td>陈皮</td>
			<td>12</td>
		</tr><tr><td>根茎 Pinelliae Preparata</td>
			<td>江板峡</td>
			<td>9</td>
		</tr></tbody></table>表1：LJZD中药物的组成和比例。
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody><tr><td>项目</td>
			<td>分级或症状</td>
			<td>分数</td>
		</tr><tr><td>减肥</td>
			<td>< 1%</td>
			<td>0</td>
		</tr><tr><td></td>
			<td>1%-5%</td>
			<td>1</td>
		</tr><tr><td></td>
			<td>5%-10%</td>
			<td>2</td>
		</tr><tr><td></td>
			<td>10%-15%</td>
			<td>3</td>
		</tr><tr><td></td>
			<td>≥15%</td>
			<td>4</td>
		</tr><tr><td>粪便潜血检测</td>
			<td>阴性</td>
			<td>0</td>
		</tr><tr><td></td>
			<td>阳性</td>
			<td>2</td>
		</tr><tr><td></td>
			<td>肉眼可见粪便带血</td>
			<td>4</td>
		</tr><tr><td>粪便稠度</td>
			<td>正常</td>
			<td>0</td>
		</tr><tr><td></td>
			<td>稀便</td>
			<td>2</td>
		</tr><tr><td></td>
			<td>水样腹泻</td>
			<td>4</td>
		</tr></tbody></table>表2：小鼠UC-CRC模型的疾病活动指数评分。

Watch this Scientific Journal Video about Author Spotlight: Liujunzi Decoction as a Traditional Chinese Treatment for Coloproctitis Cancer at JoVE.com

作者聚焦： 六君子汤作为结肠直肠炎癌症的中医治疗方法

该方案提供了由偶氮甲烷与硫酸葡聚糖钠联合诱导的溃疡性结肠直肠炎相关结直肠癌的小鼠模型。该模型用于评价中药化合物在预防和治疗结直肠癌中的疗效。

小鼠结肠直肠炎癌症模型的建立及中药治疗效果评价

Colorectal cancer (CRC) is a common malignancy of the digestive system and has become the third most common malignancy worldwide and the second leading ...

这项研究是关于用中医预防和治疗结肠直肠炎癌症的。我们旨在建立结肠直肠炎癌症的小鼠模型并评估中医指标。我们证实了中药流君子汤是预防结肠直肠炎癌症的有效方法。未来，我们将致力于识别结肠癌和直肠癌更敏感的生物标志物，并筛选流君子汤的治疗靶点。

establishment-coloproctitis-cancer-model-mice-evaluation-therapeutic

Nanyang Technological University

Research

JoVE Journal

Medicine

Establishment of Coloproctitis Cancer Model in Mice and Evaluation of Therapeutic Effect of Chinese Medicine

763 次观看.  Changchun University of Chinese Medicine. 这项研究是关于用中医预防和治疗结肠直肠炎癌症的。我们旨在建立结肠直肠炎癌症的小鼠模型并评估中医指标。我们证实了中药流君子汤是预防结肠直肠炎癌症的有效方法。未来，我们将致力于识别结肠癌和直肠癌更敏感的生物标志物，并筛选流君子汤的治疗靶点。

视频: 作者聚焦： 六君子汤作为结肠直肠炎癌症的中医治疗方法

Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer

Despite the advantages of easy applicability and cost-effectiveness, subcutaneous mouse models have severe limitations and do not accurately simulate tumor biology and tumor cell dissemination. Orthotopic mouse models have been introduced to overcome these limitations; however, such models are technically demanding, especially in hollow organs such as the large bowel. In order to produce uniform tumors which reliably grow and metastasize, standardized techniques of tumor cell preparation and injection are critical. 
We have developed an orthotopic mouse model of colorectal cancer (CRC) which develops highly uniform tumors and can be used for tumor biology studies as well as therapeutic trials. Tumor cells from either primary tumors, 2-dimensional (2D) cell lines or 3-dimensional (3D) organoids are injected into the cecum and, depending on the metastatic potential of the injected tumor cells, form highly metastatic tumors. In addition, CTCs can be found regularly. We here describe the technique of tumor cell preparation from both 2D cell lines and 3D organoids as well as primary tumor tissue, the surgical and injection techniques as well as the isolation of CTCs from the tumor-bearing mice, and present tips for troubleshooting.

We describe the establishment of orthotopic colorectal tumors via injection of tumor cells or organoids into the cecum of mice and the subsequent isolation of circulating tumor cells (CTCs) from this model.

在直肠癌原位小鼠模型中循环肿瘤细胞的分离

Despite the advantages of easy applicability and cost-effectiveness, subcutaneous mouse models have severe limitations and do not accurately simulate ...

科研

癌症研究

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer

Despite the advantages of easy applicability and cost-effectiveness, colorectal cancer mouse models based on tumor cell injection have severe limitations and do not accurately simulate tumor biology and tumor cell dissemination. Genetically engineered mouse models have been introduced to overcome these limitations; however, such models are technically demanding, especially in large organs such as the colon in which only a single tumor is desired.
As a result, an immunocompetent, genetically engineered mouse model of colorectal cancer was developed which develops highly uniform tumors and can be used for tumor biology studies as well as therapeutic trials. Tumor development is initiated by surgical, segmental infection of the distal colon with adeno-cre virus in compound conditionally mutant mice. The tumors can be easily detected and monitored via colonoscopy. We here describe the surgical technique of segmental adeno-cre infection of the colon, the surveillance of the tumor via high-resolution colonoscopy and present the resulting colorectal tumors.

A protocol for the establishment of a genetically engineered mouse model of colorectal cancer by segmental adeno-cre infection and its surveillance via high-resolution colonoscopy is presented.

遗传工程小鼠模型的散发性结肠直肠癌

Despite the advantages of easy applicability and cost-effectiveness, colorectal cancer mouse models based on tumor cell injection have severe limitations ...

Orthotopic Mouse Model of Colorectal Cancer

The traditional subcutaneous tumor model is less than ideal for studying colorectal cancer. Orthotopic mouse models of colorectal cancer, which feature cancer cells growing in their natural location, replicate human disease with high fidelity. Two techniques can be used to establish this model. Both techniques are similar and require mouse anesthesia and laparotomy for exposure of the cecum. One technique involves injection of a colorectal cancer cell suspension into the cecal wall. Cancer cells are first grown in culture, harvested when subconfluent and prepared as a single cell suspension. A small volume of cells is injected slowly to avoid leakage. The other technique involves transplantation of a piece of subcutaneous tumor onto the cecum. A mouse with a previously established subcutaneous colorectal tumor is euthanized and the tumor is removed using sterile technique. The tumor piece is divided into small pieces for transplantation to another mouse. Prior to transplantation, the cecal wall is lightly damaged to facilitate tumor cell infiltration. The time to developing primary tumors and liver metastases will vary depending on the technique, cell line, and mouse species used. This orthotopic mouse model is useful for studying the natural progression of colorectal cancer and testing new therapeutic agents against colorectal cancer.

Two techniques can be used to establish this model: injection of a cancer cell suspension into the cecal wall or transplantation of a piece of subcutaneous tumor onto the cecum. This model is useful for studying the natural progression of colorectal cancer and testing new therapeutic agents against colorectal cancer.

结直肠癌原位小鼠模型

The traditional subcutaneous tumor model is less than ideal for studying colorectal cancer. Orthotopic mouse models of colorectal cancer, which feature ...

生物学

Modeling Colitis-Associated Cancer with Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS)

Individuals with inflammatory bowel disease (IBD), such as Crohn's disease (CD) or ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC) over healthy individuals. This risk is proportional to the duration and extent of disease, with a cumulative incidence as high as 30% in individuals with longstanding UC with widespread colonic involvement.1 Colonic dysplasia in IBD and colitis associated cancer (CAC) are believed to develop as a result of repeated cycles of epithelial cell injury and repair while these cells are bathed in a chronic inflammatory cytokine milieu.2 While spontaneous and colitis-associated cancers share the quality of being adenocarcinomas, the sequence of underlying molecular events is believed to be different.3 This distinction argues the need for specific animal models of CAC.
Several mouse models currently exist for the study of CAC. Dextran sulfate sodium (DSS), an agent with direct toxic effects on the colonic epithelium, can be administered in drinking water to mice in multiple cycles to create a chronic inflammatory state. With sufficient duration, some of these mice will develop tumors.4 Tumor development is hastened in this model if administered in a pro-carcinogenic setting. These include mice with genetic mutations in tumorigenesis pathways (APC, p53, Msh2), as well as mice pre-treated with genotoxic agents (azoxymethane [AOM], 1,2-dimethylhydrazine [DMH]).5 
The combination of DSS with AOM as a model for colitis associated cancer has gained popularity for its reproducibility, potency, low price, and ease of use. Though they have a shared mechanism, AOM has been found to be more potent and stable in solution than DMH. While tumor development in other models generally requires several months, mice injected with AOM and subsequently treated with DSS develop adequate tumors in as little as 7-10 weeks.6, 7 Finally, AOM and DSS can be administered to mice of any genetic background (knock out, transgenic, etc.) without cross-breeding to a specific tumorigenic strain. Here, we demonstrate a protocol for inflammation-driven colonic tumorigenesis in mice utilizing a single injection of AOM followed by three seven-day cycles of DSS over a 10 week period. This model induces tumors with histological and molecular changes closely resembling those occurring in human CAC and provides a highly valuable model for the study of oncogenesis and chemoprevention in this disease.8

Modeling Colitis-Associated Cancer with Azoxymethane AOM and Dextran Sulfate Sodium DSS

We demonstrate a protocol in which administration of the genotoxic agent azoxymethane (AOM) followed by three cycles of the pro-inflammatory agent dextran sulfate sodium (DSS) rapidly and consistently generates colon tumors in mice with morphologic and molecular similarities to those seen in human colitis-associated cancer.

建模结肠炎相关的癌症与​​氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）

Individuals with inflammatory bowel disease (IBD), such as Crohn's disease (CD) or ulcerative colitis (UC) are at increased risk of developing colorectal ...

医学

Flexible Colonoscopy in Mice to Evaluate the Severity of Colitis and Colorectal Tumors Using a Validated Endoscopic Scoring System

The use of modern endoscopy for research purposes has greatly facilitated our understanding of gastrointestinal pathologies. In particular, experimental endoscopy has been highly useful for studies that require repeated assessments in a single laboratory animal, such as those evaluating mechanisms of chronic inflammatory bowel disease and the progression of colorectal cancer. However, the methods used across studies are highly variable. At least three endoscopic scoring systems have been published for murine colitis and published protocols for the assessment of colorectal tumors fail to address the presence of concomitant colonic inflammation. This study develops and validates a reproducible endoscopic scoring system that integrates evaluation of both inflammation and tumors simultaneously. This novel scoring system has three major components: 1) assessment of the extent and severity of colorectal inflammation (based on perianal findings, transparency of the wall, mucosal bleeding, and focal lesions), 2) quantitative recording of tumor lesions (grid map and bar graph), and 3) numerical sorting of clinical cases by their pathological and research relevance based on decimal units with assigned categories of observed lesions and endoscopic complications (decimal identifiers). The video and manuscript presented herein were prepared, following IACUC-approved protocols, to allow investigators to score their own experimental mice using a well-validated and highly reproducible endoscopic methodology, with the system option to differentiate distal from proximal endoscopic colitis (D-PECS).

Over the past few years, new generation endoscopes have emerged as important diagnostic research aids for evaluating murine colitis and colorectal tumors. We present herein a detailed protocol for endoscopic assessment of inflammation and colorectal tumors in mice, as well as a novel scoring system that uses decimal identifiers to document the endoscopic severity of colitis and colorectal tumors.

灵活的结肠镜检查在小鼠使用经过验证的内镜评分系统来评估结肠炎和结肠直肠肿瘤的严重程度

The use of modern endoscopy for research purposes has greatly facilitated our understanding of gastrointestinal pathologies. In particular, experimental ...

Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer

Over the last decade, more sophisticated preclinical colorectal cancer (CRC) models have been established using patient-derived cancer cells and 3D tumoroids. Since patient derived tumor organoids can retain the characteristics of the original tumor, these reliable preclinical models enable cancer drug screening and the study of drug resistance mechanisms. However, CRC related death in patients is mostly associated with the presence of metastatic disease. It is therefore essential to evaluate the efficacy of anti-cancer therapies in relevant in vivo models that truly recapitulate the key molecular features of human cancer metastasis. We have established an orthotopic model based on the injection of CRC patient-derived cancer cells directly into the cecum wall of mice. These tumor cells develop primary tumors in the cecum that metastasize to the liver and lungs, which is frequently observed in patients with advanced CRC. This CRC mouse model can be used to evaluate drug responses monitored by microcomputed tomography (&#181;CT), a clinically relevant small-scale imaging method that can easily identify primary tumors or metastases in patients. Here, we describe the surgical procedure and the required methodology to implant patient-derived cancer cells in the cecum wall of immunodeficient mice.

This protocol describes the orthotopic implantation of patient-derived cancer cells in the cecum wall of immunodeficient mice. The model recapitulates advanced colorectal cancer metastatic disease and allows for the evaluation of new therapeutic drugs in a clinically relevant scenario of lung and liver metastases.

小鼠患者来源的癌细胞原位植入概括了晚期结直肠癌

Over the last decade, more sophisticated preclinical colorectal cancer (CRC) models have been established using patient-derived cancer cells and 3D ...

Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice

Animal models of inflammatory bowel disease (IBD) and colorectal cancer (CRC) have provided significant insight into the cell intrinsic and extrinsic mechanisms that contribute to the onset and progression of intestinal diseases. The identification of new molecules that promote these pathologies has led to a flurry of activity focused on the development of potential new therapies to inhibit their function. As a result, various pre-clinical mouse models with an intact immune system and stromal microenvironment are now heavily used. Here we describe three experimental protocols to test the efficacy of new therapeutics in pre-clinical models of (1) acute mucosal damage, (2) chronic colitis and/or colitis-associated colon cancer, and (3) sporadic colorectal cancer. We also outline procedures for serial endoscopic examination that can be used to document the therapeutic response of an individual tumor and to monitor the health of individual mice. These protocols provide complementary experimental platforms to test the effectiveness of therapeutic compounds shown to be well tolerated by mice.

We describe methods for longitudinal monitoring of the efficacy of therapeutics for the treatment of colonic pathologies in mice using a rigid endoscope. This protocol can be readily used for the characterization of the therapeutic response of an individual tumor in live mice and also for monitoring potential disease relapse.

新的治疗肠道病变的疗效，使用活体小鼠的串行内镜成像的非侵入性评估

Animal models of inflammatory bowel disease (IBD) and colorectal cancer (CRC) have provided significant insight into the cell intrinsic and extrinsic ...

Murine Distal Colostomy, A Novel Model of Diversion Colitis in C57BL/6 Mice

Diversion colitis (DC) is a frequent clinical condition occurring in patients with bowel segments excluded from the fecal stream as a result of a diverting enterostomy. The etiology of this disease remains ill-defined but appears to differ from that of classical inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. Research aimed to decipher the pathophysiological mechanisms leading to the development of this disease has been severely hampered by the lack of an appropriate murine model. This protocol generates a murine model of DC that facilitates the study of the immune system's role and its interaction with the microbiome in the development of DC. In this model using C57BL/6 animals, distal parts of the colon are excluded from the fecal stream by creating a distal colostomy, triggering the development of mild to moderate inflammation in the excluded bowel segments and reproducing the hallmark lesions of human DC with a moderate systemic inflammatory response. In contrast to the rat model, a large number of genetically-modified murine models on the C57BL/6 background are available. The combination of these animals with our model allows the potential roles of individual cytokines, chemokines, or receptors of bioactive molecules (e.g., interleukin (IL)-17; IL-10, chemokine CXCL13, chemokine receptors CXCR5 and CCR7, and the sphingosine-1-phosphate receptor 4) to be assessed in the pathogenesis of DC. The availability of congenic mouse strains on the C57BL/6 background largely facilitates transfer experiments to establish the roles of distinct cell types involved in the etiology of DC. Finally, the model offers the opportunity to assess the influences of local interventions (e.g., modification of the local microbiome or local anti-inflammatory therapy) on mucosal immunity in affected and non-affected bowel segments and the on systemic immune homeostasis.

Murine distal colostomy provides a murine model for human diversion colitis, a predominantly lymphocytic colitis in colon segment excluded from the fecal stream.

小鼠远端结肠造口术, 一种新的 C57BL/6 老鼠转移性结肠炎模型

Diversion colitis (DC) is a frequent clinical condition occurring in patients with bowel segments excluded from the fecal stream as a result of a ...

Murine Appendectomy Model of Chronic Colitis Associated Colorectal Cancer by Precise Localization of Caecal Patch

The human appendix has been recently implicated to play important biological roles in the pathogenesis of various complex diseases, such as colorectal cancer, inflammatory bowel disease, and Parkinson&#8217;s disease. To study the function of the appendix, a gut disease-associated murine appendectomy model has been established and its step-by-step protocol is described here. This report introduces a facile protocol for caecal patch removal in mice followed by the chemical induction of chronic colitis-associated colorectal cancer using a combination of dextran sulfate sodium (DSS) and azoxymethane (AOM). IgA specific cells and IgA concentration were significantly reduced upon removal of the caecal patch in male C57BL/6 mice&#160;compared to those in the sham group. Simultaneously administering 2% DSS and AOM resulted in nearly 80% mice survival in both sham and appendectomy groups without significant body weight loss. Histological results confirmed colonic inflammation and different degrees of adenocarcinoma. This model can be used for the study of the functional role of the appendix in maintaining gut microbiota homeostasis and pathogenesis of gut colitis and malignancies, as well as for the potential development of drug targeting therapies.

The presented protocol describes a facile surgical removal of the appendix (caecal patch) in a mouse followed by the induction of inflammatory bowel disease-associated colorectal cancer. This murine appendectomy model enables investigation of the biological role of the appendix in the pathogenesis of human gastrointestinal disease.

慢性结肠炎相关结肠直肠癌的肿瘤切除术模型，通过卡卡贴片的精确定位

The human appendix has been recently implicated to play important biological roles in the pathogenesis of various complex diseases, such as colorectal ...

Impact of Sanleng Jiashen Formula on Orthotopic Hepatocellular Carcinoma in Mice

Establishment of Hepatocarcinoma in BALB/c-nu Mice and Investigation of the Therapeutic Effect of the Sanleng Jiashen Formula

The lethality of liver cancer and the resistance to chemical drugs have forced the search for effective prescriptions of traditional herbs for liver cancer. Animal models that are repeatable, easy to manipulate, and highly mimic the pathophysiological processes of liver cancer are the prerequisite for the successful screening of effective drug candidates. Meanwhile, reliable drug efficacy evaluation indicators and means are also the guarantee of anti-liver cancer drug research and development.
Sanleng Jiashen formula, a representative prescription of traditional Chinese medicine containing Sparganium stoloni erum, Buch. -Ham. (Sanleng), Panax ginseng C. A. Mey. (ginseng), Rheum officinale Baill. (rhubarb), and Ligusticum chuanxiong Hort. (Chuanxiong), is prescribed to nourish the liver and clear heat, remove toxins, and promote blood circulation to treat liver cancer. This experimental protocol describes the preparation of lyophilized Sanleng Jiashen formula and the establishment process of in-situ liver cancer in BALB/c-nu mice. Histopathological staining, immunohistochemical detection of cancer markers, in vivo imaging of mice, and chick embryo chorioallantoic membrane test were used to explore the inhibition and anti-angiogenesis effect of Sanleng Jiashen formula on malignant proliferation of liver cancer tissue. The data show that the Sanleng Jiashen formula can effectively resist the malignant proliferation of liver cancer tissue, which is manifested by reduced tumor mass volume, improved pathological damage, and lower levels of the cancer marker ki67.
The superior inhibition of angiogenesis also suggests that the Sanleng Jiashen formula may have the potential to treat and prevent the progression and deterioration of liver cancer. The whole experimental scheme shows a comprehensive process of traditional Chinese medicine components in the treatment of mouse liver cancer, which provides a reference for the establishment and optimization of a liver cancer model, as well as the research and development of drugs to prevent and treat liver cancer.

Here, we present the step-by-step protocol to investigate the therapeutic and vascular inhibitory effects of the Sanleng Jiashen formula on BALB/c-nu mice with orthotopic hepatocellular carcinoma.

The lethality of liver cancer and the resistance to chemical drugs have forced the search for effective prescriptions of traditional herbs for liver ...

小鼠结肠直肠炎癌症模型的建立及中药治疗效果评价

副本

摘要

探索更多视频

此视频中的章节

在直肠癌原位小鼠模型中循环肿瘤细胞的分离

遗传工程小鼠模型的散发性结肠直肠癌

结直肠癌原位小鼠模型

建模结肠炎相关的癌症与氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）

灵活的结肠镜检查在小鼠使用经过验证的内镜评分系统来评估结肠炎和结肠直肠肿瘤的严重程度

小鼠患者来源的癌细胞原位植入概括了晚期结直肠癌

新的治疗肠道病变的疗效，使用活体小鼠的串行内镜成像的非侵入性评估

小鼠远端结肠造口术, 一种新的 C57BL/6 老鼠转移性结肠炎模型

慢性结肠炎相关结肠直肠癌的肿瘤切除术模型，通过卡卡贴片的精确定位

Establishment of Hepatocarcinoma in BALB/c-nu Mice and Investigation of the Therapeutic Effect of the Sanleng Jiashen Formula

小鼠结肠直肠炎癌症模型的建立及中药治疗效果评价

副本

摘要

探索更多视频

此视频中的章节

在直肠癌原位小鼠模型中循环肿瘤细胞的分离

遗传工程小鼠模型的散发性结肠直肠癌

结直肠癌原位小鼠模型

建模结肠炎相关的癌症与​​氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）

灵活的结肠镜检查在小鼠使用经过验证的内镜评分系统来评估结肠炎和结肠直肠肿瘤的严重程度

小鼠患者来源的癌细胞原位植入概括了晚期结直肠癌

新的治疗肠道病变的疗效，使用活体小鼠的串行内镜成像的非侵入性评估

小鼠远端结肠造口术, 一种新的 C57BL/6 老鼠转移性结肠炎模型

慢性结肠炎相关结肠直肠癌的肿瘤切除术模型，通过卡卡贴片的精确定位

Establishment of Hepatocarcinoma in BALB/c-nu Mice and Investigation of the Therapeutic Effect of the Sanleng Jiashen Formula

建模结肠炎相关的癌症与氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）