肝硬化门静脉高压动物模型的实验对比研究

肝脏 ›› 2021, Vol. 26 ›› Issue (7): 732-736.

肝硬化门静脉高压动物模型的实验对比研究

胡豆豆, 任万雷, 仇莎, 姜相君

266011 山东青岛市市立医院消化内二科(胡豆豆,姜相君);青岛大学附属第二医院青岛市中心医疗集团中医一科(任万雷,仇莎)

收稿日期:2020-08-28 出版日期:2021-07-31 发布日期:2021-09-02
通讯作者: 姜相君,Email: drjxj@163.com
基金资助:
国家自然基金青年基金项目(81800543)

A comparison between two animal models of liver cirrhosis and portal hypertension

HU Dou-dou¹, REN Wan-lei², QIU Sha², JIANG Xiang-jun¹

1. Department of Gastroenterology, Qingdao Municipal Hospital 266011;
2. Department of Traditional Chinese Medicine, Qingdao Central Hospital 266042

Received:2020-08-28 Online:2021-07-31 Published:2021-09-02
Contact: JING Xiang-jun,Email: drjxj@163.com

摘要/Abstract

摘要： 目的对四氯化碳(CCl₄)化学损伤性以及胆管结扎(BDL)机械梗阻性大鼠门静脉高压模型进行比较,对两种动物模型在门静脉高压形成过程中的特点进行探讨。方法 CCl₄模型分为模型组和对照组,BDL模型分为模型组和假手术组。分别于造模后4周、8周、12周测量门静脉压力、取肝脾组织标本。从大鼠一般情况、门静脉压力数值、大体标本变化、病理形态学、体质量、肝脏湿重、脾脏湿重这几方面对两种动物模型进行比较分析。正态分布的资料以均数±标准差表示,两组比较采用t检验。结果 CCl₄组肝脏大体变化以肝叶变形、粘连为主,病理表现为纤维间隔分割肝实质,假小叶形成。而BDL组肝叶形态尚存,肝脏呈深褐色,病理表现为大量胆管增生。就门脉高压形成过程而言,CCl₄组门静脉压力呈逐渐升高趋势,与对照组相比,造模8周、12周有统计学差异(P<0.05)。BDL组门静脉压力呈现短期迅速升高趋势,造模4周、8周及12周较假手术组均明显升高且有统计学差异(P<0.05)。在体质量、肝脏湿重、脾脏湿重这几个指标中,脾脏湿重与门脉压力升高趋势一致。在CCl₄组,脾脏质量亦是逐渐增加的。而在BDL组,造模4周脾脏质量较假手术组明显增加,造模8周、12周时较假手术组有统计学差异(P<0.05)。结论两种动物模型门静脉高压形成过程及压力变化趋势不同,本文为深入认识不同原因肝硬化门静脉高压提供了实验依据。

关键词: 门脉高压, 肝硬化动物模型, 胆管结扎, 四氯化碳

Abstract: Objective To establish and evaluate two rat models of portal hypertension induced by carbon tetrachloride (CCl₄) and bile duct ligation (BDL). Methods 12 rats were randomly divided into CCl₄-induced liver injured group and a control group (N=6 in each group). Another 12 rats were divided into a BDL model group and a sham operation group (N=6 in each group). Portal pressures were measured and the liver and spleen tissue samples were taken at 4w, 8w, and 12w after the treatments. Rats in the model groups were compared with relative control groups and analyzed for general conditions, portal pressure, gross specimen changes, pathological morphologies, body mass, liver wet weight, and spleen wet weight. Normal distributed data are expressed as “mean±standard deviation”, and t test is used for the comparison between two groups. Results The major changes of livers in the CCl₄ model group were liver lobular deformation and adhesion. Fibrous septa and pseudolobules were observed as the pathological manifestation of liver parenchyma. In BDL model group, the shape of the liver lobes was still preserved, the livers were dark brown, and bile duct hyperplasia was the major pathological manifestation. In terms of the formation of portal hypertension, the portal pressure of rats in CCl₄ model group showed a gradual increase and significantly higher than that of the control group at 8w and 12w of CCl₄ treatment (P<0.05). The portal pressure of rats in BDL model group showed a short-term rapid increase, and significantly higher than those of the sham operation group at 4w, 8w, and 12w after BDL (P<0.05). Among the body mass, liver wet weight, and spleen wet weight, the increase of spleen wet weight is in consistent with that of portal pressure. The spleen weight of the rats of CCl₄ model group also gradually increased. The spleen weight of rats in the BDL model group was significantly higher than that of the sham operation group at 4w, and statistically different from those in the sham operation group at 8w and 12w after BDL (P<0.05). Conclusion There were differences in the formation of portal hypertension between two rat models of portal hypertension induced by carbon tetrachloride (CCl₄) and bile duct ligation (BDL). The study provides an experimental basis for further understanding of portal hypertension.

Key words: Portal Hypertension, Liver cirrhosis, Animal Models, Bile duct ligation, Carbon tetrachloride

胡豆豆, 任万雷, 仇莎, 姜相君. 肝硬化门静脉高压动物模型的实验对比研究[J]. 肝脏, 2021, 26(7): 732-736.

HU Dou-dou, REN Wan-lei, QIU Sha, JIANG Xiang-jun. A comparison between two animal models of liver cirrhosis and portal hypertension[J]. Chinese Hepatolgy, 2021, 26(7): 732-736.

参考文献

[1] Simonetto DA, Liu M, Kamath PS. Portal Hypertension and Related Complications: Diagnosis and Management. Mayo Clin Proc, 2019,94(4):714-726.
[2] Mauro E, Gadano A. What's new in portal hypertension Liver Int, 2020,40 Suppl 1:122-127.
[3] Oliver TI, Sharma B, John S. Portal Hypertension//StatPearls. Treasure Island (FL): StatPearls Publishing, 2020.
[4] Königshofer P, Brusilovskaya K, Schwabl P, et al. Animal models of portal hypertension. Biochim Biophys Acta Mol Basis Dis, 2019,1865(5):1019-1030.
[5] Bosch J, Iwakiri Y. The portal hypertension syndrome: etiology, classification, relevance, and animal models. Hepatol Int, 2018,12(Suppl 1):1-10.
[6] Rodríguez-Vilarrupla A, Fernández M, Bosch J, et al. Current concepts on the pathophysiology of portal hypertension. Ann Hepatol, 2007,6(1):28-36.
[7] Kang SH, Kim MY, Baik SK. Novelties in the pathophysiology and management of portal hypertension: new treatments on the horizon. Hepatol Int, 2018,12(Suppl 1):112-121.
[8] McConnell M, Iwakiri Y. Biology of portal hypertension. Hepatol Int, 2018, 12(Suppl 1):11-23.
[9] Wu T, Shen M, Liu S, et al. Ameliorative effect of Cyclocarya paliurus polysaccharides against carbon tetrachloride induced oxidative stress in liver and kidney of mice. Food Chem Toxicol, 2020,135:111014.
[10] Liedtke C, Luedde T, Sauerbruch T, et al. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects. Fibrogenesis Tissue Repair, 2013,6(1):19.
[11] Bolognesi M, Merkel C, Sacerdoti D, et al. Role of spleen enlargement in cirrhosis with portal hypertension. Dig Liver Dis, 2002, 34(2):144-150.
[12] Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology, 2013, 144(1):102-111.
[13] Berzigotti A, Zappoli P, Magalotti D, et al. Spleen enlargement on follow-up evaluation: a noninvasive predictor of complications of portal hypertension in cirrhosis. Clin Gastroenterol Hepatol, 2008,6(10):1129-1134.
[14] Hayashi H, Beppu T, Okabe H, et al. Combined measurements of serum bile acid level and splenic volume may be useful to noninvasively assess portal venous pressure. J Gastroenterol, 2012,47(12):1336-1341.
[15] Terayama N, Makimoto KP, Kobayashi S, et al. Pathology of the spleen in primary biliary cirrhosis: an autopsy study. Pathol Int,1994,44(10-11):753-758.