基于ROS-PARP/GAPDH途径探讨滋阴补肾活血法对视网膜微血管周细胞的保护作用研究

糖尿病视网膜病变（DR）是最常见的糖尿病并发症，具有极强的致盲性，但防治困难。课题组前期研究以“肾虚血瘀”为DR基本病机，采用滋阴补肾活血治法组方，临床疗效独特；进一步研究发现，该方能抑制内皮祖细胞VEGF/KDR环而降低血管新生。高血糖致细胞线粒体产生过量活性氧自由基（ROS），导致糖尿病血管病变，而VEGF与ROS密切相关；视网膜微血管周细胞（RMPs）是血管生成和血管功能的重要调节细胞，在DR中作为首发的受损细胞，已成为研究热点。因此，我们提出：滋阴补肾活血法能通过对ROS上游信号途径PARP/GAPDH的平衡调节，下调PARP活性，上调GAPDH活性，抑制ROS生成，保护RMPs，从而起到治疗DR的作用。本课题组拟采用HCS、FCM、激光共聚焦等技术，从在体-体外两方面、形态-功能-分子三水平，探明滋阴补肾活血方治疗DR的分子机制，揭示其作用特点与规律，为DR有效防治提供新思路。

Diabetic retinopathy (DR) is the most common complication of diabetes and has very strong blinding, but it is difficult to prevent and cure.Previous study of this research group used "Kidney Deficiency Blood Stasis" as the basic pathogenesis of DR,and the clinical therapeutic effect of prescription for nourishing yin and invigorating kidney and activating blood is effective and unique. Further research found that this formula can inhibit the endothelial progenitor cells VEGF/KDR ring and reduce angiogenesis.Hyperglycemia leads to the production of excess active oxygen free radicals (ROS) in cell mitochondria, resulting in diabetic angiopathy,and VEGF is closely related to ROS;Retinal microvascular pericytes (RMPs) are important regulators of angiogenesis and vascular function and as the first damaged cells in DR, have become a research hotspot. Thus,we propose: Nourishing Yin and Invigorating Kidney and Promoting Blood can play a important role in the treatment of DR by regulating the PARP/GAPDH signal pathway upstream of ROS, down-regulating PARP activity, up-regulating GAPDH activity and inhibiting ROS production and protecting RMPs.This group intends to use HCS, FCM and Laser Confocal techniques to explore the molecular mechanism of nourishing yin and invigorating kidney and promoting blood to treat DR and to reveal its characteristics and rules from the two aspects of in vivo and in vitro and three levels of morphology-function -molecular,which provides new ideas for effective prevention and treatment of DR.