高糖环境调节半月板细胞自噬机制研究

项目名称： 高糖环境调节半月板细胞自噬机制研究

项目编号： No.81472118

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 沈超

作者单位： 上海交通大学

项目金额： 72万元

中文摘要： 糖尿病人群中骨关节炎发病率和半月板损伤率高于正常人群，但其原因不明。我们分别证实了高糖刺激对于细胞的毒性作用以及自噬在半月板修复和退变中的保护作用，但这两者之间的相互作用未见文献报道。在前期工作中，我们发现高糖环境可以抑制大鼠半月板细胞的自噬水平,但其调节机制以及与半月板退变的关系尚不明确。本课题首先在细胞水平分别从AMPK、mTOR和JNK途径角度探究高糖环境对于半月板细胞自噬的调节机理，并观察其对于半月板细胞表型的影响;进一步采取膝关节退变动物模型在细胞和器官水平探讨高糖环境对于正常或退变半月板自噬的作用，并观察改变细胞基础自噬水平后半月板在高糖环境的代谢变化。此外，我们还对糖终末产物AGEs对于半月板细胞自噬和代谢的影响加以研究，并使用RNA干扰技术观察IP3R1在AGEs诱导半月板细胞自噬以及退变过程中的作用。拟为临床治疗糖尿病患者骨关节炎提供理论依据和实验基础。

中文关键词： 半月板；细胞自噬；高糖；细胞凋亡

英文摘要： The diabetes patients have a high risk of getting osteoarthritis and meniscus injury. However the mechanism is unclear. Our previous studies showed that the high glucose level had a toxic effect on normal cells. We also proved the protective role of autophagy in the degenerative process of meniscus. But the interacting between high glucose level and autophagy has never been investigated. Our results showed that high glucose suppressed autophagy activity in rat meniscal cells, but the mechanism was unknown. The aim of the current study is to investigate the effects of AMPK, mTOR as well as JNK signal pathway on high glucose-suppressed autophagy. The changes of the phenotypes of the meniscal cells cultured in high glucose medium were recorded. The animal model of knee osteoarthritis was also used to determine the effect of autophagy on the meniscal tissue of diabetic rats. Furthermore, the effects of advanced glycation end products (AGEs) on the metabolism and the changes of autophagy were also investigated. The role of IP3R1 on AGEs-induced autophagy was also measured via RNA interference technique. We expect the conclusion of the current study could provide new thoughts for the treatment of osteoarthritis in diabetes patients.

英文关键词： meniscus;autophagy;high glucose;apoptosis