辛伐他汀对大鼠肝纤维化的影响及其作用机制

Effects of Simvastatin on Hepatic Fibrosis in Rats and Its Mechanism

观察辛伐他汀对大鼠肝纤维化的影响并探讨其机制。60只健康的睡眠剥夺(Sleep Deprivation,SD)大鼠随机分为对照组、模型组和药物组。模型组和药物组,大鼠皮下注射四氯化碳(CCl4)油溶液造模,药物组造模同时给予辛伐他汀灌胃(5mg.kg-1.d-1)至实验结束;对照组给予等量的橄榄油皮下注射。8周后处死所有动物,全自动生化分析仪检测血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)活性,苏木精-伊红染色观察肝组织病理学改变,免疫组织化学法检测各组肝组织中I、III型胶原及转化生长因子-β1(TGF-β1)的表达情况。结果表明,与模型组相比,药物组大鼠肝脏炎症反应和纤维化较轻,I、III型胶原及TGF-β1的表达显著减少(P<0.05),血清ALT、AST水平降低(P<0.05)。由此得出,辛伐他汀可以减轻肝纤维化程度,其机制可能与抑制TGF-β1和I、III型胶原表达有关。

To observe the effects of simvastatin on hepatic fibrosis in rats and to study its possible mechanism,60 male and female SD rats were randomly divided into control group,model group,and trial group.Rats of the model group were injected with tetrachloride（CCl4）,rats of the trial group were injected with CCl4 and was gavaged with simvastatin 5mg·kg-1·d-1,and rats of the control group were injected with the equal volume of olive oil.Rats were all executed after 8 weeks,the contents of alanine aminotransferase（ALT） and aspartate aminotransferase（AST） were measured by full automatic biochemical analyzer.The pathological change of liver was observed under light microscope（hematoxylin-eosin staining）.The expression of collagen I（Col I）,collagen III（Col III）,and Transfer Growth Factor-β1（TGF-β1） were detected by immunohistochemistry.The results show that comparing the trial group with the model group,the inflammation and fibrosis are decreased in pathological sections,the expressions of Col I,Col III and TGF-β1 in the liver tissues are remarkably decreased（P0.05）,the contents of ALT and AST are decreased（P0.05）.Simvastatin can inhibit liver fibrosis induced by CCl4.The mechanism may be attributed to its effect of downregulating TGF-β1,Col I and Col III.