糖尿病肾损伤的中枢调控机制研究

Diabetic nephropathy has received extensive attention because it easily leads to end-stage renal disease and the cost of treatment is high.The pathogenic mechanism of diabetic nephropathy is complicated, however, there is still a lack of studies on central regulatory mechanism of renal injury.In this project, based on the rat model of diabetic nephropathy,central regulatory mechanism of renal injury in diabetic nephropathy will be studied using techniques of blocking central and peripheral renin-angiotensin system (RAS),reactive oxygen species(ROS),sympathetic nerve activity or Endothelin 1 receptors,and immunohistochemistry, western blot, enzyme-linked immunosorbent assay and radioimmunoassay, etc.The association of RAS, ROS, sympathetic nerve activity and Endothelin 1 level in key brain regions with those in kidney will be comprehensively studied, thus elucidating mechanism on central regulation of kidney.The association of the above parameters in brain ans kidney with renal injury will be explored, thus illustrating central regulatory mechanism of renal injury in diabetic nephropathy.The association of activation of cerebral-reno RAS/ROS axis with renal injury will be comprehensively investigated, thus elucidating molecular mechanism of regulation of renal injury by cerebral-reno RAS/ROS axis. This will lay the theoretical and experimental basis for development of diabetic nephropathy treatment with independent intellectual property rights.

糖尿病肾病因其易导致终末期肾病和高昂的治疗费用而受到广泛关注和重视。糖尿病肾病发病机制复杂，但目前有关其肾损伤中枢调控机制的研究仍很缺乏。本项目以糖尿病肾病大鼠为模型，通过脑和外周肾素-血管紧张素系统（RAS）、活性氧（ROS）、交感神经和内皮素受体等阻断技术，用免疫组织化学、蛋白质印迹、酶联免疫吸附和放射免疫分析等方法，研究糖尿病肾损伤的中枢调控机制。系统研究糖尿病肾病大鼠关键脑区的RAS、ROS、交感活性和内皮素1水平与肾脏此类指标的关系与规律性，阐明糖尿病肾病中枢对肾脏的调控机制。系统研究脑-肾上述指标与肾损伤的关系与规律性，阐明糖尿病肾损伤的中枢调控机制。系统研究脑-肾RAS/ROS轴活化与糖尿病肾损伤的的关系与规律性，阐明脑-肾RAS/ROS轴调控肾损伤的分子机制，为开发具有自主知识产权的糖尿病肾病防治奠定理论和实验基础。

糖尿病肾病因其易导致终末期肾病和高昂的治疗费用而受到广泛关注和重视。糖尿病肾病发病机制复杂，但目前有关其肾损伤中枢调控机制的研究仍很缺乏。本项目以糖尿病肾病大鼠为模型，通过脑和外周肾素-血管紧张素系统（RAS）、活性氧（ROS）、交感神经和内皮素受体等阻断技术，用免疫组织化学、蛋白质印迹、酶联免疫吸附和放射免疫分析等方法，研究了糖尿病肾损伤的中枢调控机制。系统研究了糖尿病肾病大鼠关键脑区的RAS、ROS、交感活性与肾脏此类指标的关系与规律性，阐明糖尿病肾病中枢对肾脏的调控机制。系统研究脑-肾上述指标与肾损伤的关系与规律性，阐明糖尿病肾病肾损伤的中枢调控机制。系统研究了脑-肾RAS/ROS轴活化与糖尿病肾病肾损伤的的关系与规律性，阐明了脑-肾RAS/ROS轴调控肾损伤的分子机制，为开发具有自主知识产权的糖尿病肾病防治奠定了理论和实验基础。