从PI3K/Akt/mTOR通路调控细胞自噬探讨益智仁-乌药治疗糖尿病肾病肾阳虚证的作用机制

Early prevention and treatment are very important for DN. Formulars mainly composed of YizhiRen and Wuyao are widely used to treat kindey yang deficiency DN.Our previous studies have shown that Petroleum ether fraction be the effective fractions of compatibility Yizhiren and Wuyao for anti-diabetic nephropathy, but its mechanism is still not clear. Autophagy is mainly by the aging of the damaged organelles and macromolecular substances such as protein degradation and maintain environmental stability and the integrity of the cells in the cell, Studies have shown that autophagy in the elderly and kidney injury animal model of kidney has a protective effect. The occurrence of autophagy and the DN jointly by some regulation of signaling pathways is one of the more classic PI3K/Akt/mTOR signaling pathways. We aim to study the process of autophagy in couplet medicines of YizhiRen and Wuyao by both overall experiments and in vitro experiments, and also to explore the mechanism of warming kidney and tonifying Yang of YizhiRen and Wuyao for treating The kindey yang deficiency syndrome of DN from aspects of PI3K/Akt/mTOR signaling pathway and autophagy body size and quantity, expression level of autophagy related proteins LC3 - II, Atg5, Beclin 1, P62. we discussed how Tonify kidney yang therapeutic principle works on kidney yang deficiency DN, and provide theory basis for the use of couplet medicines of YizhiRen and Wuyao in treatment of DN.

DN的早期防治是非常重要的，临床上以益智仁、乌药为主的方剂在DN肾阳虚证早期的多尿期有着广泛的应用。我们前期研究表明药对“益智仁-乌药”的石油醚提取部位在治疗DN肾阳虚证中有较好的肾脏保护作用，但是其作用机制仍未阐明。自噬主要是通过对受损细胞器和老化蛋白质等大分子物质进行降解而维持细胞内环境稳定及细胞的完整性，研究表明自噬对老年和肾损伤的动物模型的肾脏有保护作用，自噬与DN的发生共同受到PI3K/Akt/mTOR信号通路的调控。本研究拟通过体内外研究，从PI3K/Akt/mTOR信号通路变化及自噬体大小、数量、自噬相关蛋白LC3-II、Atg5、Beclin-1和P62的表达水平，研究益智仁-乌药（温补肾阳法）干预DN肾阳虚证的作用机制，为益智仁-乌药在临床治疗DN 提供理论依据。

糖尿病肾病的早期防治尤为重要，以益智仁、乌药为主的方剂在DN早期临床应用广泛，其对肾脏具有较好的保护作用，但是作用机制不清。自噬主要是通过对受损细胞器和老化蛋白质等大分子物质进行降解而维持细胞内环境稳定及细胞的完整性，研究表明自噬对老年和肾损伤的动物模型的肾脏有保护作用，自噬与DN的发生共同受到PI3K/Akt/mTOR信号通路的调控。本项目研究通过体内外实验，从PI3K/Akt/mTOR信号通路调控及自噬通量、自噬相关蛋白LC3-II、Atg5、Beclin-1和P62的表达水平，研究益智仁-乌药（温补肾阳法）干预DN肾阳虚证的作用机制，为益智仁-乌药配伍治疗DN 提供理论依据。项目研究结果表明，益智仁-乌药可通过调控自噬通量，影响自噬相关分子的mRNA和蛋白表达，影响PI3K/Akt/mTOR信号通路实现对DN(肾阳虚证)的调控，发挥对DN肾小球系膜细胞的保护作用。项目研究结果对揭示益智仁-乌药配伍治疗DN的作用机制具有重要意义。