复合致病因素诱导肝硬化大鼠TGF-α和TGF-β1的动态变化  

Dynamic changes of TGF-α and TGF-β1 in rats with liver cirrhosis induced by multiple pathogenic factors

作　　者：田小霞[1] 张慧英[1] 王黎敏[2] 李旭炯[3] 刘燕[3] 张丽丽[1] 毕杨辉 

机构地区：[1]长治医学院病理生理学教研室,山西长治046000 [2]长治医学院机能综合实验室,山西长治046000 [3]长治医学院生理学教研室,山西长治046000

出　　处：《中国应用生理学杂志》2016年第1期65-68,共4页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金资助项目(81070339);山西省国际科技合作计划资助项目(2010081068);山西省回国留学人员科研基金资助项目(211-091);山西省高等学校大学生创新创业训练项目(2014308)

摘　　要：目的:观察复合致病因素诱导肝硬化大鼠肝组织中转化生长因子-α(TGF-α)和转化生长因子-β1(TGF-β1)的动态变化。方法:采用复合致病因素法复制大鼠肝硬化模型:首次皮下注射CCl4原液(0.5 ml/100 g·w),之后每隔3天皮下注射40%CCl4油溶液(0.3 ml/100 g·w),同时辅以低胆碱、高胆固醇、高脂肪、高醇饮食。随机将大鼠分为肝硬化模型4周、6周和8周组,并分别设立同期正常对照组。检测各组大鼠血浆中谷丙转氨酶(ALT)、内毒素、肿瘤坏死因子-α(TNF-α)和同型半胱氨酸(Hcy)的水平;肝组织切片行HE染色,TGF-α和TGF-β1的免疫组化染色。结果:与相应的同期正常对照组比较,大鼠血浆中ALT、内毒素、TNF-α和Hcy水平在肝硬化模型4周、6周和8周组均逐渐显著升高(P<0.05);肝组织中TGF-α的表达在肝硬化模型4周组明显增加(P<0.05),而肝组织中TGF-β1的表达则随着肝硬化病程的进展持续显著增加(P<0.05)。结论:在肝硬化形成过程中,TGF-α的表达先增加后被抑制,TGF-β1的表达持续增加,导致肝细胞再生先增强后被抑制,而肝纤维化程度不断加重,最终发生肝硬化。TGF-α和TGF-β1的这一特征性动态变化可能与内毒素血症、TNF-α水平增高以及高同型半胱氨酸血症有关。Objective： To explore the dynamic changes of transforming growth factor-α （TGF-α） and transforming growth factor-β1 （TGF- β1） of liver cirrhosis induced by multiple pathogenic factors in rats. Methods： Animals in the cirrhosis group were fed a mixture of maize flour, lard, cholesterol and alcohol plus subcutaneously injection with carbon tetrachloride （CCl4）, the CC[4（0,5ml/100g·w） was injected at the first day of experiment and the 40% CCl4 oil solution （0.3 ml/100 g·w） was injected at an interval of three days. The thirty-six male SD rats were randomly divided into liver cirrhosis group of the 4th, 6th and 8th week, and normal control group of the 4th, 6th and 8th week. The contents of alanine transferase （ALT）, endotoxin, tumor necrosis factor-α （TNF-α） and homocysteine （Hcy） in plasma were evaluated. Histopathological changes of the liver were observed under microscope with the staining of HE. The expressions of TGF-α and TGF-β1 were analyzed by the method of immunohistochemistry. Results： Compared with the corresponding normal control group, the levels of ALT, endotoxin, TNF-α and Hcy in plasma were gradually significantly increased in liver cirrhosis group of the 4^th, 6^th and 8^th week （ P 〈 0.05） ; the expression of TGF-α in the liver tissues was significantly increased at the 4th week （ P 〈 0.05） ; the expression of TGF-131 in the liver tissues was gradually significantly increased in every model group （P 〈 0. 05）. Conclusion： In the formation process of cirrhosis, the expression of TGF-α was increased in liver of cirrhosis group at the 4th week, and later it was suppressed; the expression of TGF-β1 was continuously increased. The characteristic dynamic changes of TGF-α and TGF-β1 might be related to sustained endotoxemia, the high level of TNF-α and hyperhomocysteinemia.

关 键 词：肝硬化 肝再生 肝纤维化 TGF-Α TGF-Β1 大鼠 

分 类 号：R363[医药卫生—病理学]