肝纤维化大鼠联合门静脉离断与肝脏离断的二步肝切除术模型的建立

肝癌电子杂志 ›› 2022, Vol. 9 ›› Issue (2): 1-6.

• 论著 • 下一篇

肝纤维化大鼠联合门静脉离断与肝脏离断的二步肝切除术模型的建立

张军伟¹, 杨旭¹, 王云超¹, 王艳宇¹, 荀梓宇¹, 程全成², 方金玉², 丁慧如², 孟杰依², 张磊¹, 徐意瑶¹, 桑新亭¹, 赵海涛¹, 张卫光^2,*, 卢欣^1,*

1.中国医学科学院北京协和医学院北京协和医院肝脏外科,北京 100730;
2.北京大学医学部基础医学院解剖学与组织胚胎系,北京 100191

收稿日期:2022-03-07 发布日期:2022-10-26
通讯作者: ^*卢欣,E-mail：luxin@pumch.cn;张卫光,E-mail：zhangwg@bjmu.edu.cn
作者简介:张军伟,中国医学科学院北京协和医学院,北京协和医院,肝脏外科
基金资助:
中国医学科学院医学与健康科技创新工程项目（2021-1-I2M-061）

Establishment of a rat model: associating liver partition and portal vein ligation for staged hepatectomy with hepatic fibrosis

Zhang Junwei¹, Yang Xu¹, Wang Yunchao¹, Wang Yanyu¹, Xun Ziyu¹, Cheng Quancheng², Fang Jinyu², Ding Huiru², Meng Jieyi², Zhang Lei¹, Xu Yiyao¹, Sang Xinting¹, Zhao Haitao¹, Zhang Weiguang^2,*, Lu Xin^1,*

1. Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China;
2. Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing 100191, China

Received:2022-03-07 Published:2022-10-26

摘要/Abstract

摘要： 目的：通过四氯化碳（CCl₄）和乙醇综合法建立联合门静脉离断与肝脏离断的二步肝切除术（associating liver partition and portal vein ligation for staged hepatectomy,ALPPS）的肝纤维化模型,探讨ALPPS应用于肝纤维化大鼠的安全性及可行性。
方法：将40只雄性SD大鼠采用抽签法随机均分为对照组和肝纤维化组,每组各20只。对照组大鼠进行常规饲养,并采用橄榄油注射4周。肝纤维化组大鼠采用40%CCl₄的橄榄油溶液背部皮下注射+饮用10%乙醇4周。肝纤维化组和对照组各取5只大鼠,进行天狼猩红染色判断肝纤维化的程度。其余15只大鼠行ALPPS,并于术后即刻、第3天、第6天各取5只大鼠,取再生肝脏称重,检测肝脏增生情况,并进一步通过Ki-67免疫组织化学染色判断肝细胞再生情况。
结果：通过CCl₄和乙醇综合法建模4周,肝纤维化组大鼠体重缓慢增加,生活基本未受影响,且肝纤维化均匀,有1只大鼠因注射CCl₄死亡,建模成功率为95.0%。肝纤维化组和对照组大鼠在ALPPS后均实现了剩余肝脏体积的快速增长,且两组差异无统计学意义（P>0.05）。肝纤维化组和对照组大鼠肝组织的Ki-67阳性细胞均在术后第3天明显增多,术后第6天明显减少。
结论：采用CCl₄背部皮下注射和乙醇综合法可以快速建立肝纤维化大鼠模型,在此基础上进行ALPPS是安全可行的。本研究建立了稳定高效的肝纤维化大鼠ALPPS模型。

关键词: 肝纤维化, 联合门静脉离断与肝脏离断的二步肝切除术, 四氯化碳, 乙醇, 大鼠

Abstract: Objective:To establish the liver fibrosis model of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) by carbon tetrachloride (CCl₄) and ethanol, and to explore the feasibility and safety of ALPPS in rats with liver fibrosis.
Method:Totally 40 male SD rats were randomly allocated by lot into two groups with 20 rats in each group. The control group was the blank group, which was routinely fed and injected with olive oil for 4 weeks, and the liver fibrosis group was CCl₄ subcutaneous injection + forced drinking of 10% ethanol for 4 weeks. 5 rats in the liver fibrosis group and the control group were stained with Sirius red to judge the degree of liver fibrosis. The remaining 15 rats underwent ALPPS operation, and the regenerated liver was weighed on the 0, 3 and 6 days after operation to detect the liver proliferation, and was further judged by the hepatocyte regeneration by Ki-67 staining.
Result:After 4 weeks of CCl₄ and ethanol modeling, the weight of rats increased slowly, their life was basically unaffected, and liver fibrosis was uniform. One rat died due to the injection of CCl₄, and the success rate of liver fibrosis modeling was 95.0%. Liver fibrosis group and control group achieved rapid growth of residual liver volume after ALPPS, and there was no significant difference between the two groups. Ki-67 positive cells in hepatic fibrosis group and normal group increased significantly on the 3rd day after operation and decreased on the 6th day after operation.
Conclusion:Using the method of CCl₄ back subcutaneous injection and drinking ethanol, the liver fibrosis rat model can be established quickly. ALPPS operation is safe and feasible in this fibrosis model. In this study, a stable and efficient ALPPS rat model with liver fibrosis was established.

Key words: Liver fibrosis, Associating liver partition and portal vein ligation for staged hepatectomy, Carbon tetrachloride, Ethanol, Rat

张军伟, 杨旭, 王云超, 王艳宇, 荀梓宇, 程全成, 方金玉, 丁慧如, 孟杰依, 张磊, 徐意瑶, 桑新亭, 赵海涛, 张卫光, 卢欣. 肝纤维化大鼠联合门静脉离断与肝脏离断的二步肝切除术模型的建立[J]. 肝癌电子杂志, 2022, 9(2): 1-6.

Zhang Junwei, Yang Xu, Wang Yunchao, Wang Yanyu, Xun Ziyu, Cheng Quancheng, Fang Jinyu, Ding Huiru, Meng Jieyi, Zhang Lei, Xu Yiyao, Sang Xinting, Zhao Haitao, Zhang Weiguang, Lu Xin. Establishment of a rat model: associating liver partition and portal vein ligation for staged hepatectomy with hepatic fibrosis[J]. Electronic Journal of Liver Tumor, 2022, 9(2): 1-6.

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肝纤维化大鼠联合门静脉离断与肝脏离断的二步肝切除术模型的建立

Establishment of a rat model: associating liver partition and portal vein ligation for staged hepatectomy with hepatic fibrosis

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