两种实验性肝纤维化大鼠模型肝脏组织学特点的比较研究

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (7): 747-751.

两种实验性肝纤维化大鼠模型肝脏组织学特点的比较研究

华晓萍^{1, 2}, 张莉², 黄利², 谭正怀², 陈庄¹

¹ 泸州医学院附属医院医学实验中心,泸州 646000,四川;
² 四川省中医药科学院药理毒理研究所,成都 610041,四川

收稿日期:2013-11-12 修回日期:2014-06-05 发布日期:2014-07-21
通讯作者: 陈庄,男,博士,硕士研究生导师,研究方向:免疫病理学。Tel: 13550888750 　E?mail: zhuangchen@hotmail.com
作者简介:华晓萍,女,本科,工程师,研究方向:药理学及病理学。 Tel: 13688382747 E-mail: polly0927@sina.com

Morphological differences of liver between two liver fibrosis models induced by dimethylnitrosamine and thioacetamide

HUA Xiao-ping^{1, 2}, ZHANG Li², HUANG Li², TAN Zheng-huai², CHEN Zhuang²

¹ Experimental Medicine Center, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, Sichuan, China;
² Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, Sichuan,China

Received:2013-11-12 Revised:2014-06-05 Published:2014-07-21

摘要/Abstract

摘要： 目的对二甲基亚硝胺(DMN)及硫代乙酰胺(TAA)诱导的肝纤维化进行形态学比较。方法 0.5%DMN腹腔注射(2 mL/kg,每周3次,连续4周)或自由饮用TAA水溶液(0.03% TAA饮用9周后改用 0.04%TAA饮用6周)两种方法制备大鼠肝纤维化模型,在造模完成后,恢复4周,比较两种造模方法成功率、肝内胶原沉着情况及α-肌动蛋白(α-SMA)表达情况。结果 DMN造模动物死亡率高(>30%),TAA模型无动物死亡;DMN模型纤维化严重程度较一致,造模成功率均较TAA模型高(P<0.01);DMN模型胶原沉着面积与TAA模型相当;DMN模型α-SMA 表达高于TAA模型(P<0.01)。结论腹腔注射DMN法诱导肝纤维化优于自由摄取TAA法。

关键词: 二甲基亚硝胺, 硫代乙酰胺, 肝纤维化, 形态学

Abstract: AIM: To compare the morphological differences of liver between the two liver fibrosis models induced by dimethylnitrosamine(DMN) and thioacetamide(TAA). METHODS: 0.5% DMN (2 mL/kg; 3 times/week) was injected into the abdominal cavity of SD rats for 4 weeks to create one kind of liver fibrosis model.To create another kind of liver fibrosis models, 0.03% TAA in drinking water was administered orally to SD rats for 9 weeks and then 0.04% TAA was administered orally to SD rats for other 6 weeks. After being treated with DMN or TAA, animals were not treated for 4 weeks for recovery. The morphology of liver was evaluated in two models based on the H&E stain and the severity of liver fibrosis was compared in two models with collagen volume fraction and the protein expression of α-SMA.RESULTS: The mortality of rat in the model induced by DMN was high(30%)but no animal was dead in the model induced by TAA. The success rate in the model induced by DMN were higher than those induced by TAA (P<0.01). And the uniformity of liver fibrosis severity in the model induced by DMN is better than the latter. The two models had the similar collagen volume fractions. The protein expression of α-SMA in the model induced by DMN was higher than that induced by TAA (P<0.01).CONCLUSION: The model induced by DMN is better than that induced by TAA.

Key words: dimethylnitrosamine, thioacetamide, liver fibrosis, morphological difference

中图分类号:

R965.2

华晓萍, 张莉, 黄利, 谭正怀, 陈庄. 两种实验性肝纤维化大鼠模型肝脏组织学特点的比较研究[J]. 中国临床药理学与治疗学, 2014, 19(7): 747-751.

HUA Xiao-ping, ZHANG Li, HUANG Li, TAN Zheng-huai, CHEN Zhuang. Morphological differences of liver between two liver fibrosis models induced by dimethylnitrosamine and thioacetamide[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(7): 747-751.

参考文献

[1] 仝欣,陈高峰,陆雁,等. 基于均匀设计分析黄芪汤活性组分抗二甲基亚硝胺大鼠肝纤维化的配伍作用[J].中国中西医结合杂志,2011,31(10):1389-1393.
[2] 宛莹,张世东,贲亮,等. 脐带源间充质干细胞(hUMSCs)对硫代乙酰胺诱导肝纤维化干预作用的研究[J].中国实验诊断学,2013,17(6):1003-1005.
[3] 史丹鹤. 益生菌对硫代乙酰胺所致肝纤维化大鼠的预防作用及其机制的研究[D].山西医科大学,2012.
[4] 黄亮,陈志良,李亦蕾,等. 甘草甜素联合苦参碱对TAA引致大鼠肝纤维化的抑制作用[J]. 中药材,2012,34(11):1836-1839.
[5] 闫晓风,刘平,孙明瑜,等. 黄芪汤对二甲基亚硝胺诱导大鼠肝纤维化模型作用的机制[J]. 世界华人消化杂志,2010,18(23) : 2410-2415.
[6] Gu K, Zhao JD, Ren ZG, et al.A natural process of cirrhosis resolution and deceleration of liver regeneration after thioacetamide withdrawal in a rat model[J]. Molecular Biology Reports, 2011,38(3): 1687-1696.
[7] 罗时敏,谭卫民,庄思敏,等. 硫代乙酰胺诱导的肝硬化大鼠蛋白质代谢变化[J]. 中国医师杂志,2005,7(7): 919-921.
[8] Friedman SL.Mechanisms of disease: Mechanisms of hepatic fibrosis and therapeutic implications. Clin Pract Gastroenterol Hepatol[J]. 2004,1(2):98-105.
[9] Tomasek JJ, Gabbiani G, Hinz B, et al.Myofibroblasts and mechano-regulation of connective tissue remodeling[J]. Mol Cell Biol,2002,3(5):349-363.
[10] Wynn TA.Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases[J]. Clin Invest,2007,117(3):524-529.
[11] Wynn TA.Cellular and molecular mechanisms of fibrosis[J]. Pathol,2008,214(2):199-210.
[12] 杨文卓,曾民德. 肝纤维化的发生机制及病理生理[J].国外医学消化系疾病分册,2000,20(4):216-221.
[13] Friedman SL.Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver[J]. Physiol ,2008,88(1): 125-172.
[14] 周伟,沈薇. 肝细胞增殖、凋亡与肝纤维化关系的实验研究[J]. 重庆医学,2007,36(11):1062-1064.

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