葡萄糖调节蛋白78在大鼠非酒精性脂肪性肝炎中的表达及意义

Expression and significance of glucose regulated protein GRP78 in nonalcoholic steatohepatitis of rats

目的观察高脂饮食诱导大鼠非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)过程中内质网应激标志物葡萄糖调节蛋白78的表达变化,探讨内质网应激在NASH发病机制中的作用。方法建立大鼠高脂饮食诱导NASH模型,检测血清ALT、AST、FFA、TG和肝组织MDA的变化,用RT-PCR与Western blot方法检测NASH形成过程中肝组织GRP78在基因和蛋白水平的表达变化。结果NASH组大鼠血清ALT、AST、FFA、TG和肝组织MDA水平均较对照组有不同程度的升高。肝组织GRP78基因和蛋白表达也随NASH加重而增强,16周时升高最为显著(P<0.01)。结论高脂饮食可诱导GRP78表达增强,启动内质网应激,导致脂质异常沉积,其可能与NASH的发病机制密切相关。

Objective To investigate the expression of endoplasmic reticulum molecular chaperone, glucose regulated protein 78 （ GRP78 ）, in the liver tissues during fatty diet-induced nonalcoholic steatohepatitis （NASH） in rats and explore the role of endoplasmic reticulum stress in pathogenesis of nonalcoholic steatohepatitis. Methods Rat model of nonalcoholic steatohepatitis were established with fatty dieting. Blood samples were collected to detect serum aspartate transaminase （AST）, alanine aminotransferase （ALT）, free fatty acid （FFA） and triglyceride （TG）. Liver tissues were obtained to measure malondialdehyde （MDA） content. The expression of GRP78 in the liver was detected with RT-PCR and Western blot analysis. Results Compared with the control group, the serum contents of ALT, AST, FFA and TG and liver content of MDA in NASH were increased. The expression of GRP78 at protein and gene levels were increased in NASH in a time-dependent manner, and reached peak in 16 weeks （ P 〈 0.01 ）. Conclusion Enhanced expression of GRP78 could be induced by fatty diet. The excessive expression of GRP78 could result in the endoplasmic reticulum stress, and thus lead to fatty acid abnormal deposition, which might be closely involved in NASH.