grp78,srebp-1c在非酒精性脂肪性肝病发病 - 第三军医大学学报.doc

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 闵敏，陈东风 \（第三军医大学大坪医院野战外科研究所消化内科，重庆 400042） 摘要：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。 关键词：非酒精性脂肪性肝炎；内质网应激；葡萄糖调节蛋白78 Expression and significance of endoplasmic reticulum molecular chaperone GRP78 in nonalcoholic steatohepatitis in rats Min-Min, CHEN Dong-feng (Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China) Abstract: Objective To investigate the expression of endoplasmic reticulum molecular chaperone 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 diet.Blood samples were collected for the detection of serum aspartate transaminase (AST),alanine aminotransferase (ALT),free fatty acid（FFA）and triglyceride（TG）.Liver tissues were obtained for the measured of the malondialdehyde 基金项目:国家自然科学基金 Supported by the National Science Foundation of China 作者简介:闵敏，女，湖北天门人，硕士研究生，主要从事非酒精性脂肪性肝病方面的研究。电话通讯作者:陈东风，E-mail:chendf1981@126.com (MDA) contents.The expression of GRP78 in the liver was detected with RT-PCR and Western blot. Result Compared with the control group,the content of serum ALT、AST、FFA、TG and MDA in NASH were increased in different level and as well as the expression of GRP78 protein and gene in NASH,its peak was reached in 16 week(P0.01).Conclusion Enhanced expression of GRP78 could be induced by fatty diet.The excessive expression of GRP78 could result in the t