项目名称: 基于PERK内质网应激信号通路探讨黄芩素在糖尿病肾病中的抗凋亡机制
项目编号: No.81202818
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 医学八处
项目作者: 孙惠力
作者单位: 广州中医药大学
项目金额: 23万元
中文摘要: 肾组织细胞凋亡在糖尿病肾病蛋白尿形成和病情进展中发挥重要作用,内质网应激是诱导细胞凋亡重要的上游事件,PERK是内质网应激重要信号通路之一,PERK-CHOP信号通路活化在肾脏疾病中发挥促凋亡作用。中药单体黄芩素在非肿瘤性组织细胞表现为抗凋亡作用。本项目基于课题组的前期工作:即黄芩素对糖尿病大鼠肾脏具有一定保护作用,糖尿病大鼠肾组织存在PERK内质网应激信号通路活化的研究结果,拟采用RNA干扰技术下调PERK基因表达,并应用黄芩素进行干预,通过体内和体外实验,观察其对糖尿病肾组织细胞凋亡的影响。旨在明确PERK内质网信号通路活化在糖尿病肾组织细胞凋亡的作用,及黄芩素的糖尿病肾脏保护作用是否依赖于其对PERK信号通路的抑制效应。本课题的意义在于为糖尿病肾病的中药防治提供新靶点,并阐明黄芩素的部分糖尿病肾病保护机制。
中文关键词: 糖尿病肾病;黄芩素;内质网应激;炎症;
英文摘要: Renal cell apoptosis is thought to contribute to proteinuria production and the disease progress of diabetic nephropathy.Endoplasmic reticulum stress(ERS) is an upstream event of apoptosis.PERK is one of the endoplasmic reticulum stress signaling pathways and PERK-CHOP pathway play a proapoptotic role in kidney disease. Chinese herb monomer baicalein exert anti-apoptotic activites for non-neoplastic cells. Our previous results demonstrated that baicalein ameliorate renal injury in experimental diabetes and PERK endoplasmic reticulum stress signaling pathway is activated in diabetic kidney.In this study,PERK is down-regulated by PERK siRNA,and baicalein is then used to interfere in vivo and in vitro.The effct of PERK for the cell apoptosis in diabetic kidney was investigated.The objective of this study is to clarify the role of PERK pathway activation for cell apoptosis in diabetic kidney,and to define whether diabetic renal protective effect of baicalein is dependent on its inhibition of the PERK signaling pathway. The significance of this project is to provide new targets Chinese medicine prevention for diabetic nephropathy,and to clarify the partial mechanisms that baicalein protect the diabetic kidney.
英文关键词: diabetic nephropathy;baicailein;endoplasmic reticulum stress;inflammation;