基于IRE-1/XBP-1通路探讨益智仁-乌药干预糖尿病肾病内质网应激的作用机制

Early prevention and treatment are very important for 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.It is thought that ERS plays an important role in the development and progression of DN. The IRE-1/XBP-1 signaling pathway plays a key regulatory role in ERS. Based on this, we propose that YizhiRen and Wuyao, through intervention IRE-1/XBP-1 signaling pathway, reduce ERS and play the role of kidney protection. In this study, we intend to study the expression of IRE-1/XBP-1 signaling pathway, GRP78, ERS-related apoptotic signaling pathway (CHOP, JNK, caspase-12) by cell transfection, qPCR, Western blot and ELISIA in vitro and in vivo，As well as the impact on cell proliferation and apoptosis.From the perspective of overall, organizational and molecular level, we study the possible mechanism of YizhiRen and Wuyao in treating DN and provide the theoretical basis for YizhiRen and Wuyao in clinical treatment of DN.

DN的早期防治是非常重要的，我们前期研究证实药对“益智仁-乌药”的石油醚提取部位在治疗DN中有较好的作用，但是其作用机制仍未阐明。研究认为ERS在DN的发生发展过程中起着重要的作用，IRE-1/XBP-1信号通路在ERS中发挥关键的调节作用，据此提出益智仁-乌药通过干预IRE-1/XBP-1信号通路，减轻ERS，发挥肾脏保护作用这一假说。本研究拟通过体内外研究，用细胞转染、qPCR、Western blot和ELISIA等方法研究IRE-1/XBP-1信号通路、内质网分子伴侣GRP78、ERS相关凋亡信号通路（CHOP、JNK、caspase-12）的表达，以及对细胞增殖、细胞凋亡的影响。从整体、组织、分子水平研究益智仁-乌药治疗DN的可能机制，为益智仁-乌药在临床治疗DN提供理论依据。

本项目从IRE-1/XBP-1信号通路角度探索了益智仁-乌药药对通过干预内质网应激治疗糖尿病肾病的作用机制。研究发现，益智仁-乌药药对可抑制IRE-1/XBP-1信号通路，从而抑制细胞内质网应激，抑制肾小球系膜细胞增殖，保护肾小球足细胞。研究结果为益智仁-乌药药对治疗糖尿病肾病的临床应用提供了理论依据和基础实验证据支持。本项目研究发表论文3篇，其中SCI 收录1篇，北大核心2篇。培养研究生1名。