视网膜炎症损伤是糖尿病视网膜病变（DR）致盲的关键原因，申请人前期研究发现该过程由NLRP3炎症小体介导，预实验进一步显示DR患者NLRP3启动子区域显著低甲基化，且沉默甲基化转移酶DNMT3b后，NLRP3表达增加。研究已证实LncRNAH19可通过与SAHH相互作用而抑制DNMT3b表达，因此我们提出LncRNAH19/SAHH/DNMT3b可通过介导NLRP3低甲基化在DR炎症损伤中发挥重要作用。本课题拟从NLRP3上游调控机制着手，分析DR患者中LncRNAH19/SAHH/DNMT3b表达水平及NLRP3甲基化程度与DR炎症损伤的关系，同时通过上调及下调LncRNAH19/SAHH/DNMT3b通路相关分子及功能挽救实验，在人视网膜微血管内皮细胞和STZ大鼠DR模型中验证其通过调控NLRP3低甲基化诱导DR炎症损伤的发生机制，有望为DR的防治提供新的干预手段。

Retinal inflammatory injury is the key cause of blindness in diabetic retinopathy (DR). Our previous studies have identified that there was enhanced expression of NLRP3 inflammasome-related inflammation in DR patients, which mediates the retinal inflammatory injury. Through further investigation, we found that NLRP3 was hypomethylated in promoter region, and the expression of NLRP3 was increased after DNMT3b gene was silenced. Since studies have confirmed that LncRNA H19 can inhibit the expression of DNMT3b by interacting with SAHH, we proposed that LncRNA H19/SAHH/DNMT3b can play a key role in the inflammatory injury of DR by mediating NLRP3 hypomethylation. This project intends to start from the upstream regulatory mechanism of NLRP3 and analyze the relationship between the expression level of LncRNA H19/SAHH/DNMT3b and the methylation level of NLRP3 and the inflammatory injury in DR patients. At the same time, through up-regulation and down-regulation of LncRNA H19/SAHH/DNMT3b pathway related molecules and functional rescue experiments, the mechanism of DR inflammatory injury induced by LncRNA H19/SAHH/DNMT3b-mediated NLRP3 hypomethylation was verified in retinal microvascular endothelial cells and STZ diabetic rat models, which is expected to provide new intervention means for DR prevention and treatment.