牛磺脱氧胆酸抑制内质网应激介导的细胞凋亡保护糖尿病肝损伤的研究

项目名称： 牛磺脱氧胆酸抑制内质网应激介导的细胞凋亡保护糖尿病肝损伤的研究

项目编号： No.81501839

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 周琪

作者单位： 吉林大学

项目金额： 18万元

中文摘要： 内质网应激（ERS）介导的凋亡途径在糖尿病肝损伤（DLI）发病中的作用引起人们重视，抗ERS成为治疗糖尿病并发症的新选择。课题组前期研究证实1型糖尿病小鼠肝脏中存在ERS及细胞凋亡、且纤维化增强，但在1型糖尿病小鼠模型中ERS与DLI发病机制的研究、调控ERS对模型DLI的发病及高糖环境下对肝细胞的影响尚未明确。本研究采用免疫印迹法、超声检查、免疫组化法、细胞培养、生化及免疫等方法，使用1型糖尿病小鼠肝脏及体外培养的人肝癌细胞系HepG2细胞，在内质网应激抑制剂牛磺脱氧胆酸（TUDCA）干预下进行ERS信号通路及细胞凋亡的研究，探讨TUDCA是否通过抑制ERS预防糖尿病诱导的肝细胞凋亡，是否抑制肝功障碍及肝纤维化，阐明TUDCA保护DLI的机制。该研究将为DLI的预防和治疗措施选择提供重要理论支持，将为研发治疗DLI药物开辟一条新途径。

中文关键词： 糖尿病肝损伤；1型糖尿病；内质网应激；牛磺脱氧胆酸；凋亡

英文摘要： Endoplasmic reticulum stress (ERS)-mediated apoptosis is involved in the pathogenesis of diabetic liver injury (DLI). The anti-ERS treatment has become the new choice of treatment of diabetic complications. Our previous studies showed ERS and apoptosis existed in type 1 diabetic mouse liver and diabetes resulted in fibrosis. However, the relationship between ERS and the pathogenesis of DLI in type 1 diabetic mouse model, and the effects of ERS regulation on DLI and hepatocytes incubation with high glucose have not been reported previously. The present study was undertaken to define whether ERS inbibitor tauroursodeoxycholic acid (TUDCA) can inhibite diabetic hepatic cell death, liver dysfuntion and fibrosis via suppression of ERS in type 1 diabetes. We will evaluate the ERS signal pathway and apoptosis with intervention of tauroursodeoxycholic acid in type 1 diabetic mouse liver and cultured human hepato carcinoma cell line HepG2. The methods include Western blotting, immunohistochemistry, ultrasonography, cell culture, biochemistry and immunology. The study could provide important theoretical support for prevention and treatment of DLI. The study also might open up a new way for the drugs in research and development for DLI.

英文关键词： diabetic liver injury;type 1 diabetic;endoplasmic reticulum stress;tauroursodeoxycholic acid;apoptosis