基于PARP通路探讨益气活血中药治疗糖尿病周围神经病变的分子机制

项目名称： 基于PARP通路探讨益气活血中药治疗糖尿病周围神经病变的分子机制

项目编号： No.81473464

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： 李鸣镝

作者单位： 中国中医科学院广安门医院

项目金额： 72万元

中文摘要： 糖尿病周围神经病变(DPN)是高血糖导致的缺血性神经细胞损伤。高糖引起的细胞内氧化应激参与了损伤过程。ROS、PKC、NF-κB的活化是氧化应激通路的三个关键因素,而PARP活化是DPN发病的关键因素之一。针对DPN气虚血瘀病机，我们应用益气活血中药治疗DPN已有20多年临床研究积累。前期研究发现该方可降低DPN神经组织炎性因子表达，此效应与PARP关系密切，故推测该方治疗DPN的可能机制，是通过影响PARP、ROS、PKC、NF-κB的活化而发挥作用，抑制PARP活化可能是该方作用的关键。本研究采用免疫组化、透射电镜、激光共聚焦、RT-PCR、神经电生理等技术，从整体、细胞及分子水平等不同层面探讨该方治疗DPN的疗效特点及分子机制，验证该假说的客观性。结果可为中医益气活血防治DPN提供新的理论和实验依据，为传承名老中医经验提供新思路。

中文关键词： 糖尿病周围神经病变；PARP；益气活血法；分子机制

英文摘要： Diabetic peripheral neuropathy (DPN) is ischemic neuronal injury caused by hyperglycemia. Intracellular oxidative stress induced by high glucose involved in the injury process. Activation of ROS, PKC and NF-κB is three key factors for oxidative stress pathway, and the activation of PARP is one of the key factor of DPN. To aim at DPN pathogenesis of blood stasis due to Qi deficiency, we have over 20 years of clinical research in application of replenishing Qi and activating blood traditional Chinese medicine in treating DPN. Through the previous research it was found that the prescription may reduce the expression of inflammatory factors of DPN nerve tissue, and this effect is closely correlated with PARP, so it is speculated that the possible mechanism in treatment of DPN is to play a role through effecting activation of PARP, ROS, PKC, and NF-κB, inhibiting PARP activation may be the key of this prescription. By immunohistochemistry, electron microscopy, Laser Confocal, RT-PCR, electrophysiological techniques, exploring the treatment of DPN clinical features and molecular mechanisms from an overall, cellular and molecular levels at different aspects done in this research to verify the objectivity of the hypothesis. A new theoretical and experimental basis for DPN prevention and cure through replenishing Qi and activating blood by traditional Chinese medicine provided in this research, and new ideas for inheritance of experience of famous veteran TCM doctors offered.

英文关键词： DPN;PARP;replenishing Qi and activating blood;Molecule mechanism