TUDCA通过抑制内质网应激及氧化应激减轻CCl_(4)所致小鼠急性肝损伤

TUDCA alleviates acute liver injury in mice induced by CCl_(4) treatment by inhibiting ER stress and oxidative stress

目的:探讨牛磺熊去氧胆酸(TUDCA)对小鼠急性肝损伤的保护机制。方法:采用小鼠腹腔注射四氯化碳(CCl_(4))诱导急性肝损伤动物模型,通过测定血清转氨酶变化及观察肝组织切片HE染色,检测TUDCA对小鼠急性肝损伤的保护效果;采用硫代巴比妥酸(TBA)法检测血清中丙二醛(MDA)的含量及羟胺法检测血清中超氧化物歧化酶(SOD)活性;采用蛋白免疫印迹、PCR等方法检测肝组织中免疫球蛋白重链结合蛋白(Bip)、肌醇需求酶1(IRE1)、c-Jun氨基末端激酶(JNK)蛋白以及X盒结合蛋白1(XBP1)基因转录表达的变化,分析TUDCA对急性肝损伤的保护机制。结果:TUDCA显著保护由CCl_(4)中毒引发的肝组织病变,与单独急性肝损伤相比,TUDCA预处理显著增强肝组织的抗氧化水平,并抑制内质网应激程度。结论:TUDCA通过抑制由CCl_(4)中毒引发的内质网应激和氧化应激,对急性肝组织损伤具有显著保护作用。

Objective:To investigate the hepatoprotective mechanisms of tauroursodeoxycholic acid(TUDCA)on acute liver injury in mice induced by carbon tetrachloride(CCl_(4)).Methods:The acute hepatotoxicity model was induced by intraperitoneal injection of CCl_(4) in mice.To investigate the protective effect of TUDCA on hepatic injury,the activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were characterized and the tissue sections were analyzed by haematoxylin-eosin(H&E)stain.To further explore the potential protective mechanisms of TUDCA on hepatic injury,we measured the contents of malondialdehyde(MDA),the activity of superoxide dismutase(SOD)in mice serum,and analyzed the expressions of binding immunoglobulin protein(Bip),inositol-requiring kinase 1(IRE1),cJUN N-terminal kinase(JNK)and X-box binding protein-1(XBP1).Results:Hepatic steatosis was observed in the livers of CCl 4 treated mice as compared to the control group,whereas the mice pretreated with TUDCA showed approximately normal liver architecture.TUDCA inhibited the elevated ALT and AST activities and decreased the accumulation of ROS.In addition,CCl_(4)-induced ER stress in mice livers could be inhibited by TUDCA.Conclusion:TUDCA alleviates CCl_(4)-induced acute liver injuries by reducing ROS accumulation and by suppression of the ER stress.