胡黄连苦苷Ⅱ抗大鼠肝纤维化的作用研究

Effect of PicrosideⅡon Anti-hepatofibrosis in Rats

背景:胡黄连苦苷Ⅱ可治疗急性肝损伤,但对肝纤维化的作用尚不明。目的:探讨胡黄连苦苷Ⅱ对CCl_4致大鼠肝纤维化的治疗作用及其机制。方法:采用CCl_4腹腔注射诱导大鼠肝纤维化模型,56只大鼠分为正常对照组、模型组、胡黄连苦苷Ⅱ治疗组和胡黄连苦苷Ⅱ对照组。造模第8周,处死大鼠。以HE染色和Masson染色观察肝组织改变和肝纤维化程度,以电子显微镜观察超微结构变化,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、白蛋白(ALB)以及组织丙二醛(MDA)水平,以逆转录聚合酶链反应(RT-PCR)和免疫组化法分别检测肝组织转化生长因子(TGF)-β1、Ⅰ型胶原mRNA和蛋白表达。结果:与正常对照组相比,模型组肝组织炎症和纤维化程度、血清ALT、AST以及肝组织MDA水平、TGF-β1和Ⅰ型胶原mRNA和蛋白表达显著增高,血清ALB水平显著降低,超微结构发生显著改变。经胡黄连苦苷Ⅱ治疗后,上述指标均显著改善,但与正常对照组相比差异仍有统计学意义。胡黄连苦苷Ⅱ对照组上述各项指标与正常对照组无明显差异。结论:胡黄连苦苷Ⅱ可通过改善肝功能、抑制脂质过氧化反应、下调TGF-β1和Ⅰ型胶原mRNA和蛋白表达而抑制肝纤维化的形成。

Background： Picroside Ⅱ can be used to treat acute liver injury, but its effect on hepatofibrosis is not clear. Aims： To investigate the effect and mechanism of Picroside Ⅱ on hepatofibrosis induced by carbon tetrachloride （CCl4） in rats. Methods： Liver fibrosis model in rats was induced by intraperitoneal injection of CCl4. Fifty-six rats were randomly divided into 4 groups： normal control group, model group, Picroside Ⅱ treatment group and Picroside Ⅱ control group. At the end of the 8th week, all the rats were sacrificed. The hepatic pathological changes and fibrosis were observed by HE and Masson staining. Changes of ultramicrostructure were observed by electron microscope, and serum alanlne aminotransferase （ALT）, aspartate aminotransferase （AST）, albumin （ALB） and tissue malonaldehyde （MDA） were determined. The mRNA and protein expressions of transforming growth factor （TGF）-β1 and collagen type Ⅰ in liver tissue were determined by reverse transcriptase polymerase chain reaction （RT-PCR） and immunohistochemistry , respectively. Results： Compared with normal control group, the degree of inflammation and fibrosis, serum ALT, AST, tissue MDA, mRNA and protein expressions of TGF-β1 and collagen type Ⅰ were significantly increased, serum ALB was significantly decreased, significant changes of uhramicrostructure were observed in model group. After treatment with Picroside Ⅱ, all the abovementioned indices significantly ameliorated, but significant differences were still found between Picroside Ⅱ treatment group and normal control group. No significant differences were found between Picroside Ⅱ control group and normal control group in all the above-mentioned indices. Conclusions： Picroside Ⅱ can inhibit the formation of liver fibrosis probably through the improvement of liver function, inhibition of lipid peroxidation, and reduction of mRNA and protein expressions of TGF-β1 and collagen type Ⅰ .