基于HIF-1α/VEGF/Notch信号通路的藏药小檗皮对藏医“赤巴型”糖尿病视网膜血管炎症损伤的机制研究

糖尿病视网膜病（DR）已严重威胁人类健康，而抑制视网膜血管炎症可改善DR。藏医认为DR是由赤巴增盛引起的，小檗皮长于清赤巴，对DR的治疗应用颇多，但其作用机制尚不明确。前期研究发现主要含小檗皮的制剂，能降低糖尿病干眼症小鼠结膜中VEGF和炎症因子表达。本项目在藏医药理论的指导下，将小檗皮对赤巴型DR的作用与血管炎症损伤进行关联，提出“小檗皮对DR的保护作用是基于HIF-1α/VEGF/Notch通路调节血管炎症来实现的”的假说。以视网膜血管炎症为切入点，利用UPLC-Q-TOF-MS明确小檗皮调控HIF-1α/VEGF/Notch通路的物质基础；借助db/db小鼠和人视网膜微血管上皮细胞，采用激光共聚焦、流式细胞、Western Blot和qRT-PCR等手段，从“整体-细胞-分子”水平，阐明小檗皮治疗赤巴型DR血管炎症损伤的科学内涵，为探索藏药防治DR的机制研究提供新的靶点和思路。

Diabetic retinopathy (DR) is a serious threat to human health, and inhibition of retinal vascular inflammation can improve DR. It is believed that the cause of DR in Tibetan Medicine is due to the increase of mK-hrispa. Berberidis Cortex, a Tibetan medicine, is commonly used to treat the DR of mK-hrispa type. However, the mechanism for its action of inflammatory injury of diabetic retinal microvascular is poorly defined. We have found that Berberidis Cortex can significantly improve the expression of VEGF and inflammatory factors in the conjunctiva of diabetic dry eye mice. Therefore, under the guidance of the traditional Tibetan medicine theory, this project organically correlates the effect of Berberidis Cortex on the DR of mK-hrispa type with vascular inflammation injury is based on HIF-1α/VEGF/Notch" signaling pathway to regulate vascular inflammation. We take vascular inflammation as the breakthrough point. And then relate active constituents of Berberidis Cortex were analyzed by UPLC-Q-TOF-MS. Moreover, db/db mice and human retinal microvascular endothelial cells are employed to study the anti-inflammation mechanism of Berberidis Cortex in vitro and in vivo by laser scanning confocal microscope, flow cytometry, Western Blot, and qRT-PCR. We aim at investigating the mechanism of the effect of Berberidis Cortex on DR from the perspective of “whole-cell-molecule”, to clarify the scientific connotation in the treatment of vascular inflammation injury of DR. It is possible to provide new target and research idea for exploring the mechanism of traditional Tibetan medicine in the treatment of DR.