益气活血祛风除湿方调节葡萄膜炎微循环“缺氧-免疫炎症”效应的研究

葡萄膜炎多为自身免疫反应所引起的疾病，我们根据葡萄膜炎中医病机以及长期激素治疗后的气阴两虚证侯,提出治疗葡萄膜炎在调节免疫的同时需重视改善微循环缺氧的新思路，应充分考虑到益气、活血、祛风、除湿的原则，微循环缺氧的改善可缓解免疫炎症的发生。我们将通过建立EAU大鼠模型，证实益气活血祛风除湿方防治葡萄膜炎炎症的效应，验证复方可通过HIF-1α这一关键环节来改善微循环瘀滞缺氧，提出HIF-1α/VEGFA/p38-MAPK通路的存在；通过体外实验验证视网膜微血管内皮细胞在低氧环境下HIF-1α通路中相关蛋白的表达及调控关系，并将证实本项目复方可抑制HIF-1α下调VEGFA，进而减少对p38-MAPK的活化。预期本次研究的开展，将为中医药可通过改善缺氧以缓解自身免疫反应的效应提供依据和实验基础，为葡萄膜炎的防治揭示新的药物治疗靶点，为葡萄膜炎此类免疫性疾病的中药治疗策略的制定提供一个有利的参考。

Uveitis is a disease caused by autoimmune reaction with high recurrence rate.According to the pathogenesis of uveitis in traditional Chinese medicine and the syndrome of deficiency of both qi and Yin after long-term treatment with hormone, we suggest that we should pay more attention to the improvement of microcirculation hypoxia while regulating immunity in the treatment of uveitis.The principles of Invigorating Qi, promoting blood circulation, expelling wind and dehumidification should be fully considered in this treatment process. The improvement of microcirculation hypoxia can alleviate the occurrence of immune inflammation.Based on the characteristics of holistic and dialectical view of traditional Chinese medicine, we will first establish Eau rat model, in order to confirm the effect of Yiqi Huoxue Qufeng Chushi formula on the prevention and treatment of uveitis inflammation. Then we will further verify that the compound can improve microcirculation stasis and hypoxia through the key link of HIF-1α, and propose the existence of HIF-1α/ VEGFA / p38-MAPK pathway.In addition, the expression and regulation of related proteins in HIF-1 α pathway of retinal microvascular endothelial cells in hypoxia environment will be verified by experiments in vitro, and it will be confirmed that the compound of this project can inhibit HIF-1α, down regulate VEGFA, and then reduce the activation of p38-MAPK.It is expected that the development of this study will provide the basis and experimental basis for traditional Chinese medicine to alleviate the effect of autoimmune response by improving hypoxia, reveal new drug treatment targets for the prevention and treatment of uveitis, and provide a favorable thinking and reference for the formulation of traditional Chinese medicine treatment strategies for immune diseases such as uveitis.