益智仁-乌药调控线粒体氧化应激治疗肾阳虚型糖尿病肾病的机制研究

项目名称： 益智仁-乌药调控线粒体氧化应激治疗肾阳虚型糖尿病肾病的机制研究

项目编号： No.81473618

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： 谢毅强

作者单位： 海南医学院

项目金额： 75万元

中文摘要： 糖尿病肾病的早期防治非常重要，临床上以益智仁乌药为主的方剂在肾阳虚型DN 早期的多尿期有广泛应用，但机制尚不明确。线粒体氧化应激，可诱导线粒体蛋白质和DNA的结构改变，最终引起线粒体通透性转变的出现。本研究拟以整体和体外实验(高糖环境下系膜细胞的变化)两部分，从线粒体结构（Cu/Zn-SOD、Mn-SOD、GPx、thiol、PARL、MDA、蛋白质羰基）、功能（△ψm、NAD[P]H、mitochondrial electron flow）及后续MPT及CDPs释放（AIF、EndoG和Cyt c、caspase-9、caspase-3、8-oxoG DNA、mitochondrial swelling、p66Shc蛋白表达）研究益智仁-乌药温肾补阳，保护肾阳虚型DN的机制，为益智仁乌药临床治疗DN提供理论依据，并有望进一步丰富以线粒体氧化应激为切入点的DN的中医药防治手段。

中文关键词： 糖尿病肾病；肾阳虚；线粒体氧化应激；益智仁-乌药

英文摘要： Early prevention is very important for diabetic nephropathy (DN), formulas mainly composed of Yizhi Ren and Wuyao are widely used in treatment of Yang-deficiency type DN during the early period of diuresis though the mechanism are not clear. Mitochondrial oxidative stress can induce structural changes in mitochondrial proteins and DNA, ultimately causing mitochondrial permeability transition. We aim to study the process of mitochondrial oxidative stress in couplet medicines of Yizhi Ren and Wuyao by both overall experiments and in vitro experiments (changes inmesangial cells under high glucose environment), and also to explore the mechanism of warming kidney and tonifying Yang of Yizhi Ren and Wuyao for treating Yang-deficiency type DN from aspects of mitochondrial structure (Cu/Zn-SOD, Mn-SOD, GPx, thiol, PARL, MDA and protein carbonyl), function (△ψm, NAD[P] H, mitochondrial electron flow) and subsequent MPT and CDPs release (AIF, EndoG and Cyt c, caspase-9, caspase-3, 8-oxoG DNA, mitochondrial swelling, p66Shc protein expression). We are trying to provide theory basis for the use of couplet medicines of Yizhi Ren and Wuyao in treatment of DN in the hope of shedding light on TCM treatment of DN from aspect of mitochondrial oxidative stress.

英文关键词： diabetic nephropathy;kidney yang deficiency;mitochondrial oxidative stress;Yizhiren-wuyao