肝硬化大鼠TGF-α和TGF-β1变化及丹参素的作用  

Changes of TGF-αand TGF-β1 and Protective Effects of Danshensu in Rats with Liver Cirrhosis

作　　者：田小霞[1] 张慧英[1] 冀菁荃[1] 贾建桃[1] 陈云霞[2] 李宝红[1] 

机构地区：[1]长治医学院病理生理学教研室,046000 [2]长治医学院微生物学教研室

出　　处：《长治医学院学报》2014年第3期165-168,共4页Journal of Changzhi Medical College

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);山西医科大学细胞生理学省部共建教育部重点实验室主任基金资助项目(2010-09);长治医学院博士科研启动经费项目(2010-01)

摘　　要：目的:探讨复合致病因素诱导的肝硬化大鼠TGF-α和TGF-β1改变及丹参素的保护作用。方法:取24只健康雄性SD大鼠,随机分为正常对照组(8只)、肝硬化组(8只)、丹参素干预组(8只)。采用复合致病因素法复制大鼠肝硬化模型,丹参素干预组采用丹参素进行干预[0.05g/(kg·w),每日灌胃]。于实验第8周末取材;检测血浆谷丙转氨酶(ALT)、谷草转氨酶(AST)和内毒素水平;检测血浆和肝组织匀浆中肿瘤坏死因子-α(TNF-α)、转化生长因子-α(TGF-α)和转化生长因子-β1(TGF-β1)水平;肝组织切片行HE染色,观察病理学变化。结果:与正常对照组相比,肝硬化组脂肪变性明显,有典型的假小叶形成;血浆ALT、AST和内毒素水平显著升高(P<0.05);血浆和肝组织匀浆TNF-α和TGF-β1水平也显著升高(P<0.05),而TGF-α水平无明显变化。与肝硬化组相比,丹参素干预组大鼠肝纤维化程度明显减轻;血浆ALT、AST和内毒素水平显著降低(P<0.05);血浆和肝组织匀浆TNF-α和TGF-β1水平也显著降低(P<0.05),而TGF-α水平显著增高(P<0.05)。结论:在持续的肠源性内毒素作用下,TNF-α大量产生,TGF-α和TGF-β1之间失平衡,可能是复合致病因素诱导的大鼠肝硬化发病的重要机制,丹参素可以通过某种机制降低内毒素水平,减少TNF-α的产生,在一定程度上维持TGF-α和TGF-β1之间的平衡,对肝脏发挥促再生和保护作用。Objective：To explore changes of TGF-αand TGF-β1 and protective effects of Danshensu in rats with liver cirrhosis induced by multiple pathogenic factors.Methods：The twenty-four male SD rats were randomly separated into normal control group（n=8）,liver cirrhosis group（n=8）and Danshensu-treated group（n=8）.Liver cirrhosis in rats was induced by multiple pathogenic factors.The rats in Danshensu-treated group were given by Danshensu[0.05 g/（kg·w）,daily intragastric].The levels of ALT,AST and endotoxin in plasma were evaluated.The contents of TNF-α,TGF-αand TGF-β1 in plasma and in the liver tissues were detected.Histopathological changes of the liver were observed under microscope with the staining of HE.Results：Compared with normal control group,the levels of ALT,AST and en-dotoxin in plasma were significantly higher（P 〈0.05）,and the levels of TNF-αand TGF-β1 in plasma and in the liver tissues were significantly higher（P〈0.05）,but the level of TGF-αwas no significant difference in liver cirrhosis group.In Danshensu-treated group,the pathological damage of hepatic tissue was significantly attenuated,and the levels of ALT,AST and endotoxin significantly decreased（P〈0.05）,and the levels of TNF-αand TGF-β1 in plasma and in the liver tissues were significantly decreased（P〈0.05）,however,the level of TGF-αwas significantly increased（P〈0.05）compared with liver cirrhosis group.Conclusion：The findings suggest the imbalance of TGF-αand TGF-β1 may be the important pathogenesis of hepatic cirrhosis induced by multiple pathogenic factors because of the effects of sustained intestinal endotoxemia（IETM）and TNF-αin rats.Danshensu can reduce endotoxin and TNF-αvia certain mechanisms,and restore the balance between TGF-αand TGF-β1 in some degree,thereby Danshensu may exert a protective effect on hepatic cirrhosis induced by multiple pathogenic factors in rats.

关 键 词：内毒素 肝硬化 肝再生 肝纤维化 丹参素 

分 类 号：R363[医药卫生—病理学]