绞股蓝总皂苷对四氯化碳诱导的大鼠肝纤维化肝细胞凋亡的影响  

Effects of gypenosides on hepatocyte apoptosis in rats with liver fibrosis induced by carbon tetrachloride

作　　者：陈亮[1] 彭景华[1] 冯琴[1] 刘林[1] 梁春耕[1] 海亚美 胡义扬[1,2,3] 

机构地区：[1]上海中医药大学附属曙光医院.上海中医药大学肝病研究所,上海201203 [2]上海市高校中医内科学E-研究院,上海201203 [3]上海市中医临床重点实验室,上海201203

出　　处：《中华中医药杂志》2015年第1期211-215,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家科技重大专项(No.2012ZX09103-201-048);国家中医药管理局中医肝胆病重点学科~~

摘　　要：目的:观察绞股蓝总皂苷对大鼠肝纤维化的作用及其肝细胞凋亡的影响,探讨其作用机制。方法:采用四氯化碳(CCl4)诱导的大鼠肝纤维化模型共造模9周。造模6周后绞股蓝总皂苷组给予200mg/kg鼠重的绞股蓝总皂苷灌胃,而正常组和模型组正常饮水对照灌胃,共3周。观察血清丙氨酸氨基氢移酶(ALT)活性和肝组织羟脯氨酸(Hyp)含量,肝组织HE染色、天狼猩红染色、Tunel染色,以及免疫组化以及免疫组化α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(ColⅠ)蛋白表达;肝组织α-SMA、ColⅠ、转化生长因子β1(TGF-β1)、血小板源性生长因子β受体(PDGF-βR)、半胱氨酸天冬氨酸蛋白酶7(caspase 7)、半胱氨酸天冬氨酸蛋白酶9(caspase 9)、Bax、Bak、Bcl-2 m RNA表达。结果:病理观察显示绞股蓝总皂苷有显著的抗损伤和抗肝纤维化作用,与模型组比较,绞股蓝总皂苷组的大鼠血清ALT、肝组织Hyp含量显著降低(P<0.05),肝组织α-SMA、ColⅠ蛋白阳性表达及其m RNA表达显著低于模型组;Tunel染色显示绞股蓝总皂苷组凋亡的肝细胞数明显低于模型组,且TGF-β1、PDGF-βR、caspase 7、caspase 9、Bax、Bak m RNA表达较模型组显著降低(P<0.01,P<0.05),Bcl-2 m RNA表达显著升高(P<0.01)。结论:抑制线粒体通路介导的肝细胞凋亡是绞股蓝总皂苷抗肝纤维化的重要机制之一。Objective： To observe the effects of gypenosides on liver fibrosis and hepatocyte apoptosis in rats with liver fibrosis induced by carbon tetrachloride, further to investigate function mechanism. Methods： Liver fibrosis was induced by carbon tetrachloride （CCl4） injected subcutaneously twice per week for nine weeks. After six weeks building model, rats were administrated with gypenosides （200mg/kg body weight） for three weeks. The pathological changes of liver tissue, the ALT activity of serum, the content of hepatic hydroxyproline （Hyp）, the number of apoptotic hepatocytes. The protein expression of -SMA, Col I and the mRNA expressions of α -SMA, Col I, TGF- β1, PDGF- β R, caspase 7, caspase 9, Bax, Bak, Bcl-2 were observed. Results： Gypenosides had significant effect on anti-inflammatory and anti-fibrosis on pathologic changes. Compared with model group, gypenosides decreased expressions of ALT, Hyp （P〈0.05） and apoptotic hepatocytes. The protein and mRNA expressions of α -SMA and Col I decreased obviously with gypenosides in comparison with model group. Similarly, the mRNA expressions of TGF- β 1, PDGF-β R, caspase 7, caspase 9, Bax, Bak was down-regulated （P〈0.01, P〈0.05） and Bcl-2 mRNA increased remarkably compared to model group （P〈0.01）. Conclusion： The inhibition of hepatocyte apoptosis which is through mitochondrial pathway may be the key mechanism of anti-fibrosis.

关 键 词：绞股蓝总皂苷 肝纤维化 肝细胞凋亡 线粒体损伤 

分 类 号：R285.5[医药卫生—中药学]