基于PPARγ/c-Ski信号通路探究黄芩苷对乙型病毒性肝炎大鼠肝功能损伤的机制

Investigation of the mechanism of hepatic impairment by baicalin in rats with viral hepatitis B based on PPARγ/c⁃Ski signaling pathway

目的 基于PPAR-γ/cSki信号通路探究黄芩苷对乙型病毒性肝炎大鼠肝功能损伤的影响。方法 将大鼠随机分为sham组、HBV组、HQL组、HQM组、HQH组、PT组,每组10只。使用全自动生化检测仪检测血清中丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)含量,肝脂质代谢指标总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL)含量及肝纤维化指标透明质酸(HA)和层黏连蛋白(LN)含量;ELISA检测血清中一氧化碳合酶iNOS、IL-6、IL-10、IL-4水平;苏木精-伊红(HE)染色检测肝组织病理学变化;染色质免疫共沉淀法分析肝组织中病毒载量;蛋白质印迹检测肝组织中PPAR-γ和c-Ski蛋白表达。结果 和sham组相比,HBV组大鼠血清中ALT、AST、TC、TG、LDL、HA、LN、iNOS和IL-6含量均明显升高,HDL、IL-10和IL-4含量明显减少(P<0.05);和HBV组相比,HQL组、HQM组、HQH组和PT组大鼠血清中ALT、AST、TC、TG、LDL、HA、LN、iNOS和IL-6含量明显降低,HDL、IL-10和IL-4含量升高(P<0.05)。HBV组大鼠肝组织中HBV DNA及PPAR-γ、c-Ski蛋白表达高于sham组(P<0.05);和HBV组相比,HQL组、HQM组、HQH组和PT组大鼠肝组织中HBV DNA表达及PPAR-γ和c-Ski蛋白明显降低,且HQH组和PT组大鼠肝组织中的HBV DNA表达最低(P<0.05)。结论 黄芩苷能通过激活PPAR-γ/c-Ski信号抑制乙型病毒性肝炎大鼠的肝纤维化,对肝组织发挥保护作用。

Objective To investigate the effect of baicalin on liver function impairment in rats with viral hepatitis B based on PPAR⁃γ/cSki signaling pathway.Methods The rats were randomly divided into sham group,HBV group,HQL group,HQM group,HQH group and PT group,10 rats in each group.The serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST),total cholesterol(TC),triacylglycerol(TG),high⁃density lipoprotein cholesterol(HDL),low⁃density lipoprotein cholesterol(LDL)and hepatic fibrosis were measured using a fully automated biochemical assay.low⁃density lipoprotein cholesterol(LDL)and liver fibrosis indicators hyaluronic acid(HA)and laminin(LN);ELISA to detect serum levels of iNOS,IL⁃6,IL⁃10 and IL⁃4;HE staining to detect pathological changes in liver tissue;chromatin immunoprecipitation to analyze viral load in liver tissue;protein blotting to detect PPAR⁃γand c⁃Ski protein expression in liver tissue.Results Compared with the sham group,the serum levels of ALT,AST,TC,TG,LDL,HA,LN,iNOS and IL⁃6 were significantly increased and the levels of HDL,IL⁃10 and IL⁃4 were significantly decreased in the rats of the HBV group(P<0.05);com⁃pared with the HBV group,the serum levels of ALT,AST,TC,TG,LDL,HA,LN,iNOS and IL⁃6 were signifi⁃cantly decreased in the rats of the HQL,HQM,HQH and PT groups(P<0.05);compared with the HBV group,the serum levels of ALT,AST,TC,TG,LDL,HA,LN,iNOS and IL⁃6 levels were significantly decreased,and HDL,IL⁃10 and IL⁃4 levels were increased in the serum of rats in the HQL,HQM,HQH and PT groups compared with the HBV group(P<0.05).Compared with the sham group,the expression of HBV DNA and PPAR⁃γand c⁃Ski protein in the liver tissues of rats in the HBV group were significantly increased(P<0.05);compared with the HBV group,the expression of HBV DNA and PPAR⁃γand c⁃Ski protein in the liver tissues of rats in the HQL,HQM,HQH and PT groups were significantly decreased,and the liver tissues of rats in the HQH and PT groups The HBV DNA expression in the liver tissues of rats in the HQH and PT groups was the lowest(P<0.05).Conclusion Baicalin can inhibit hepatic fibrosis in rats with viral hepatitis B by activating PPAR⁃γ/c⁃Ski signaling,and exerts a protec⁃tive effect on liver tissue.