茵陈蒿汤对肝纤维化大鼠Caspase-12通路以及TIMP-1、Smad2的影响

目的探究茵陈蒿汤对肝纤维化(LF)大鼠Caspase-12通路以及TIMP-1、Smad2的影响。方法雄性SD大鼠45只,随机分为3组,即对照组,模型组和茵陈蒿汤组。使用腹腔注射CCl4建立LF模型,茵陈蒿汤组在建模时使用茵陈蒿汤灌胃,持续8周。比较8周后各组大鼠的一般情况,分别使用HE染色和Masson染色观察肝组织形态和纤维化情况。分别使用Western blot和RT-qPCR检测蛋白和mRNA的水平。结果模型组大鼠出现明显的肝损伤和纤维化,茵陈蒿汤组大鼠肝损伤情况和纤维化情况显著减轻。血生化结果显示,模型组ALT和AST水平显著高于对照组(P<0.05),菌陈蒿汤干预后ALT和AST水平显著低于模型组,差异具有统计学意义(P<0.05)。建模后8周模型组大鼠肝组织中GRP78、eIF2α和Caspase-12显著升高(P<0.01),茵陈蒿汤组的GRP78、eIF2α和Caspase-12显著低于模型组(P<0.01)。模型组的CollagenⅠ、CollagenⅢ、TIMP-1、Smad2 mRNA和蛋白水平显著高于对照组(P<0.01),茵陈蒿汤组CollagenⅠ、CollagenⅢ、TIMP-1、Smad2 mRNA和蛋白水平显著低于模型组(P<0.01)。结论茵陈蒿汤可显著缓解大鼠肝组织的纤维化,这可能由于茵陈蒿汤具有抑制Caspase-12通路以及Smad2基因的表达发挥抗纤维化和抗凋亡的作用有关。

Effects of Yinchenhao Decoction on Caspase-12 Pathway and TIMP-1 and Smad2 inRats with Hepatic Fibrosis

Objective To investigate the effects of Yinchenhao Decoction on Caspase-12 Pathway and TIMP-1 and Smad2 in Rats with Hepatic Fibrosis. Method Forty-five male Sprague-Dawley rats were randomly divided into three groups, namely, control group, model group and Yinchenhaotang group. The LF model was established by intraperitoneal injection of CCl(. The Yinchenhao decoction group was intragastrically administered with Yinchenhao soup for 8 weeks. The general situation of rats in each group was compared after 8 weeks. Liver tissue morphology and fibrosis were observed by HE staining and Masson staining, respectively. Protein and mRNA levels were determined using Western blot and RT-qPCR, respectively. Result Rats in the model group developed significant liverdamageand fibrosis.Theresultofblood biochemistryshowed thatthelevelsofALTand ASTin themodel group were significantly higher than those in the control group ( P<0. 05 ) . The levels of ALT and AST after the intervention of Yinchenhaotang, decoction were significantly lower than those in the model group (P<0. 05 ) . Liver injury and fibrosis in the Yinchenhaotang group were significantly alleviated. GRP78, eIF2& and Caspase-12 were significantly increased in the liver tissue of the model group at 8 weeks after modeling (P<0. 01 ) . GRP78, eIF2a and Caspase-12 in Yinchenhaotang group were significantly lower than those in the model group (P<0.01 ) . The mRNA and protein levels of Collagen I, Collagen III, TIMP-1 and Smad2 in the model group were significantly higher than those in the control group (P<0. 01 ) , but the mRNA and protein levels of Collagen I, Collagen III, TIMP-1 and Smad2 in Yinchenhao Decoction group were significantly lowerthan those in the modelgroup (P<0.01) . Conclusion Yinchenhao Decoction can significantly alleviate the fibrosis of rat liver tissue, which maybe related to the inhibition ofCaspase-12 pathway and the expression ofSmad2 gene in anti-fibrosis and anti-apoptosis.