茵陈蒿汤对胆汁淤积性肝纤维化大鼠内质网应激PERK通路的影响  

Experimental Study on Effects of Yinchenhao Tang(茵陈蒿汤) on Endoplasmic Reticulum Stress PERK Pathway in Cholestasis Liver Fibrosis Rats

作　　者：李木松[1] 张贵贤[1] 魏媛媛[1] 刘震霞[1] 

机构地区：[1]河北省保定市传染病医院肝五A科,河北保定071000

出　　处：《中国中医药科技》2016年第5期535-538,共4页Chinese Journal of Traditional Medical Science and Technology

基　　金：河北省保定市传染病医院人才项目(2015021)

摘　　要：目的:观察茵陈蒿汤对胆汁淤积性肝纤维化大鼠PKR样内质网激酶(PERK)-真核生物翻译起始因子(e IF2α)-转录活性因子4(ATF4)的影响,探讨茵陈蒿汤抗胆汁淤积性肝纤维的作用机制。方法:将35只SD大鼠分为假手术组和造模组,采用胆总管结扎法复制胆汁淤积性肝纤维化大鼠模型,1 W后将造模组动物分为模型组和中药组,中药组予以3.5 g/kg茵陈蒿汤灌胃,4 W后处死动物。HE、Masson染色观察肝脏组织病理学变化;Western blot法检测各组大鼠肝脏PERK、e IF2α和ATF4蛋白表达的变化。结果:肝脏组织病理学变化显示模型组大鼠肝纤维化程度较假手术组明显增加(P<0.05),中药组大鼠肝纤维化程度较模型组减轻(P<0.05),但仍重于假手术组。Western blot结果显示,模型组肝脏PERK、e IF2α和ATF4蛋白的表达与假手术组相比显著升高(P<0.01),中药组较模型组PERK、e IF2α和ATF4蛋白表达明显降低(P<0.01)。结论:抑制PERK、e IF2α和ATF4的活化,从而减少肝细胞凋亡,进而抑制内质网应激在胆汁淤积性肝纤维化中的促进作用,是茵陈蒿汤抗胆汁淤积性肝纤维化的作用机制之一。Objective： To observe the effects of Yinchenhao Tang on endoplasmic reticulum stress PKR-like ER kinase（ PERK）,eukaryotic translation initiation factor- 2alpha（ e IF2α） and transcription activity factor4（ ATF4） pathway of cholestasis liver fibrosis rat and explore the mechanism. Methods： 35 SD rats were divided into sham operation group and model group. The common bile duct ligation method was used to build the cholestasis liver fibrosis models.. After building 1 week,models were divided into model group and Chinese medicine group. Chinese medicine group was given 3. 5g / kg Yinchenhao Tang by intragastric administration for four weeks. HE and Masson staining were used to observe the pathologic changes of rats＇ liver tissue; Western blot method to detect PERK,e IF2α and ATF4 protein expression changes in rats＇ liver tissue. Results： The liver fibrosis rat model was duplicated successfully. The degree of liver fibrosis in the Chinese medicine group was lower than that in the model group（ P〈0. 05）,but it was more severe than that in the sham operation group. Blot Western showed that the expression of PERK,e IF2α and ATF4 in the model group were significantly higher than those in the sham operation group（ P〈0. 01）,and those in the Chinese medicine group were significantly decreased（ P〈0. 01）. Conclusion ： Inhibition of PERK,e IF2α and ATF4 activation,resulting in reduced apoptosis of liver cells,thereby inhibiting the promoting effect of ERS in the liver fibrosis of bile stasis,which is one action mechanism of Yinchenhao Tang anti bile stasis liver fibrosis.

关 键 词：肝硬化 胆汁性 菌陈蒿汤 @内质网激酶 大鼠 

分 类 号：R285.5[医药卫生—中药学]