基于炎性细胞-血管内皮crosstalk探讨绿原酸改善糖尿病视网膜病早期病变的作用机制

糖尿病视网膜病(DR)是临床上最常见、最严重慢性发展的糖尿病微血管并发症之一。近年来中国糖尿病患者持续增多，已跃居世界首位，DR患病率也随之日益增长，成为成年人致盲的主要原因。中药金银花和菊花常被制成具有清暑热、利嗓、明目护眼功效的保健茶饮。绿原酸是金银花、菊花的主要活性成分，前期研究发现绿原酸可以缓解视网膜炎性损伤，逆转血-视网膜屏障破损，改善DR早期病变。本课题拟在此基础上，从抑制高糖状态下小胶质细胞中ERK1/2-NFkappaB介导的炎性反应、激活Nrf2缓解炎性诱导的视网膜血管内皮表型转化和氧应激损伤以及进一步反馈性抑制视网膜炎性渗出，揭示绿原酸通过调控炎性细胞-视网膜血管内皮间对话，维持炎性-视网膜血管稳态平衡，抑制血-视网膜屏障破损，改善DR早期病变的机制。通过课题实施为金银花、菊花传统明目活性和绿原酸在DR治疗中的潜在应用提供实验依据，也为DR病变机制的研究探索建立新思路。

Diabetic retinopathy (DR) is one of the most common and severe microvascular complications of diabetes mellitus (Diabetes, DM). In recent years, the number of diabetes in China continues to increase, and it has already leaped to the first place in the world. Meanwhile, the prevalence of DR is also increasing, and it has become the main reason for causing the blindness in adults. Lonicerae Japonicae Flos (Jin-Yin-Hua) and Chrysanthemi Flos (Ju-Hua) are traditionally used for clearing away heat and toxic materials. Lonicerae Japonicae Flos and Chrysanthemi Flos are commonly made into health-care teas with clearing summer-heat, beneficial to the throat and eyesight-improving capacity. Chlorogenic acid (CGA) is the main active compound in Lonicerae Japonicae Flos and Chrysanthemi Flos. In the previous study, we found that chlorogenic acid reduced retinal inflammation and attenuated blood-retinal barrier (BRB) breakdown, and thus alleviated the development of non-proliferative DR (NPDR), which is the early stage of DR. Based on the previous research, the present study aims to elucidate the alleviation of NPDR provided by CGA via attenuating BRB breakdown through maintaining the homeostasis of retinal inflammation-microvascular endothelium via regulating the crosstalk between immune cells and retinal microvascular endothelial cells by inhibiting ERK1/2-NFkappaB-initiated inflammation in microglia, reversing the oxidative stress injury and the endothelial to mesenchymal transition (EndoMT) induced by inflammation through activating Nrf2 in retinal microvascular endothelial cells and the subsequent feedback inhibition on retinal inflammatory cells exudation. The results will provide the experimental evidences for the traditional eyesight-improving activity of Lonicerae Japonicae Flos and Chrysanthemi Flos, and the potential application of CGA for DR treatment in clinic. This study will also provide a new strategy for studying the involved mechanism of DR development.