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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
【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。
【Abstract】 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[0.05g/(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 endotoxin 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.
【Key words】 endotoxin; liver cirrhosis; liver regeneration; liver fibrosis; Danshensu;
- 【文献出处】 长治医学院学报 ,Journal of Changzhi Medical College , 编辑部邮箱 ,2014年03期
- 【分类号】R575.2
- 【被引频次】5
- 【下载频次】98