补阳还五汤调控AD神经血管单元RAGE/LRP1受体系统的分子机制研究

The treatment of Alzheimer's disease (AD) is always a tough problem of the medical field. It is an effective way to search the drug for AD therapy from traditional Chinese medicine, which has a multi-component, multi-target and little toxic and side-effect. Bu Yang Huan Wu Tang can reinforce Qi, activate blood circulation and activate collaterals. Our preliminary study results showed that Bu Yang Huan Wu Tang could significantly improve the learning and memory impairment of AD rat model, through recovering neurons and microvascular damage caused by Aβ deposition. Abnormal transporting across the blood-brain barrier of Aβ is the central link of AD pathogenesis. Transporter Aβ (RAGE and LRP1) help Aβ thansport cross the blood-brain barrier. Based on previous work, RAGE / LRP1 receptor system was as an entry point, the neurovascular unit (NVU) was as research system, this subject would carried out both in vivo and in vitro tests, through neuropathology and molecular biology techniques to study the AD NVU protection role of Bu Yang Huan Wu Tang. At the same time, by ELISA, real-time quantitative PCR and Western blot analysis, the main molecular proteins and mRNA expression of RAGE/LRP1 receptor system would be detected, designed to clarify the mechanism of Bu Yang Huan Wu Tang on NVU protection, to clarify the targets of Bu Yang Huan Wu Tang on prevention and treatment of AD, and to lay the foundation of research and development for clear targets of anti-AD traditional Chinese drugs.

AD的治疗一直是医学界的难题，从中药中寻找多成分、多靶点、毒副作用小的AD治疗药物是一种有效途径。补阳还五汤具补气活血、通经活络之功效，前期研究结果表明，补阳还五汤对AD模型大鼠学习记忆障碍具有明显改善作用，显著地改善Aβ沉积所造成的神经元和微血管损害。Aβ 跨血脑屏障的转运异常是AD发病的中心环节。Aβ跨血脑屏障转运主要由Aβ转运体(RAGE及LRP1)来完成。本课题拟以RAGE /LRP1受体系统为切入点，以神经血管单元（NVU）为研究体系，从体内、外不同角度，采用神经病理学技术和分子生物学技术，探讨补阳还五汤对AD的NVU保护作用；同时采用ELISA、实时定量PCR和Western blot技术，检测RAGE/LRP1受体系统中主要分子蛋白和mRNA表达水平，旨在阐明补阳还五汤对NVU的保护作用机制，明确补阳还五汤防治AD的作用靶点，为研发出作用靶点明确的抗AD中药新药奠定基础。

老年轻痴呆（AD）的治疗一直是医学界的难题，从中药中寻找多成分、多靶点、毒副作用小的AD治疗药物是一种有效途径。补阳还五汤具补气活血、通经活络之功效，前期研究结果表明，补阳还五汤对AD模型大鼠学习记忆障碍具有明显改善作用，显著地改善Aβ沉积所造成的神经元和微血管损害。Aβ 跨血脑屏障的转运异常是AD发病的中心环节。Aβ跨血脑屏障转运主要由Aβ转运体(RAGE及LRP1)来完成。本课题拟以RAGE /LRP1受体系统为切入点，以神经血管单元（NVU）为研究体系，从体内、外不同角度，采用神经病理学技术和分子生物学技术，探讨补阳还五汤对AD的NVU保护作用；同时采用ELISA、实时定量PCR和Western blot技术，检测RAGE/LRP1受体系统中主要分子蛋白和mRNA表达水平，旨在阐明补阳还五汤对NVU的保护作用机制，明确补阳还五汤防治AD的作用靶点，为研发出作用靶点明确的抗AD中药新药奠定基础。