Poldip2调控NOX4来源的H2O2在糖尿病视网膜微血管病变中的作用及机制研究

糖尿病视网膜病变（DR）是我国常见的致盲眼病。视网膜微血管病变是DR主要病理特征。课题组前期发现：Poldip2在DR视网膜微血管、高糖诱导的内皮细胞的线粒体和内质网中均高表达，且与H2O2产生显著相关；而H2O2与视网膜微血管病变显著相关；但其作用机制尚不清楚。据此，我们推测：高糖导致视网膜微血管中Poldip2高表达，激活NOX4产生过量H2O2，激活缺氧诱导因子-1α导致微血管病变，引起DR发生。课题拟以DR为研究对象，以Poldip2为切入点，以Poldip2调控NOX4-H2O2介导新血管生成的机制为轴线，明确Poldip2通过NOX4调控H2O2的作用机制，以及H2O2介导HIF-1α通路在视网膜微血管病变中的分子机制。通过此研究将揭示“Poldip2调控NOX4来源的H2O2介导HIF-1α通路在DR视网膜微血管病变作用”这一科学问题，将为DR预防和治疗提供新靶点和药物选择。

Diabetic retinopathy (DR) is a common blinding eye disease in China. Microvascular disease is the main pathological feature of DR. Our study was found that poldip2 was highly expressed in the mitochondria and endoplasmic reticulum of DR retinal microvascular and endothelial cells induced by high glucose, and was significantly related to the production of H2O2, and H2O2 was significantly related to retinal microvascular disease. However, the mechanism of its action was not clear. Therefore, we speculate that high glucose can cause high expression of poldip2 in retinal microvascular, activate NOX4 to produce excessive H2O2, activate hypoxia inducible factor-1 α to cause microvascular disease of DR. Taking DR as the research object, poldip2 as the starting point, and the mechanism of poldip2 regulating NOX4-H2O2 mediated angiogenesis as the axis, the mechanism of poldip2 regulating H2O2 through NOX4 and the molecular mechanism of HIF-1 α pathway mediated by H2O2 in retinal microvascular are clarified. This study will reveal the scientific problem that poldip2 regulates the role of H2O2 from NOX4 to mediate HIF-1 α pathway in DR microvascular disease, which will provide new targets and drug selection for DR prevention and treatment.