circ-001209调控白细胞介素-33/生长刺激表达基因2蛋白信号通路对糖尿病视网膜病变大鼠视网膜微血管生成的作用机制  

Mechanism of circ-001209 on retinal angiogenesis in rats with diabetic retinopathy by regulating interleukin-33/suppression of tumorigenicity 2 signaling pathway

作　　者：龚雨佳 李海龙 曹慧[1] GONG Yujia;LI Hailong;CAO Hui(Department of Ophthalmology,Changsha Central Hospital Affiliated to University of South China,Changsha,Hunan,410000;Department of Ophthalmology,Liuyang Jili Hospital,Changsha,Hunan,410000)

机构地区：[1]南华大学附属长沙中心医院眼科,湖南长沙410000 [2]浏阳市集里医院眼科,湖南长沙410000

出　　处：《实用临床医药杂志》2025年第4期23-28,33,共7页Journal of Clinical Medicine in Practice

基　　金：2021年湖南省自然科卫联合项目(S2021JJKWLH0012)。

摘　　要：目的探讨circ-001209调控白细胞介素-33/生长刺激表达基因2蛋白(IL-33/ST2)信号通路对糖尿病视网膜病变(DR)大鼠视网膜微血管生成的作用机制。方法将50只大鼠随机分为Col组、DR组、si-circ-NC组、si-circ-001209组和si-circ-001209+IL-33组,每组10只。检测大鼠空腹血糖(FPG)和血清空腹胰岛素(FINS)水平;采用荧光素眼底血管造影术(FFA)检测视网膜血管生成;采用酶联免疫吸附试验(ELISA)检测血清中血管生成相关因子及炎症因子水平;采用苏木精-伊红(HE)染色检测视网膜组织病理学变化;采用过碘酸-Schiff反应(PAS)染色检测视网膜微血管生成数;采用蛋白质印迹法检测视网膜组织中IL-33、ST2、血管内皮生长因子(VEGF)、低氧诱导因子-1α(HIF-1α)、细胞间黏附分子-1(ICAM-1)蛋白表达。结果与Col组比较,DR组、si-circ-NC组FPG,FINS,血清VEGF、血管生成素-1(Ang-1)、IL-6、IL-33、肿瘤坏死因子-α(TNF-α)水平,微血管生成数以及视网膜组织中IL-33、ST2、VEGF、HIF-1α、ICAM-1蛋白表达均升高,差异有统计学意义(P<0.05);si-circ-001209组FPG,FINS,血清VEGF、Ang-1、IL-6、IL-33、TNF-α水平,微血管生成数以及视网膜组织中IL-33、ST2、VEGF、HIF-1α、ICAM-1蛋白表达均低于si-circ-NC组,差异有统计学意义(P<0.05);si-circ-001209+IL-33组FPG,FINS,血清VEGF、Ang-1、IL-6、IL-33、TNF-α水平,微血管生成数及视网膜组织中IL-33、ST2、VEGF、HIF-1α、ICAM-1蛋白表达高于si-circ-001209组,差异有统计学意义(P<0.05)。结论敲减circ-001209可抑制DR大鼠视网膜微血管生成,作用机制可能与抑制IL-33/ST2信号通路激活、降低炎症水平有关。Objective To investigate the mechanism of circ-001209 on retinal angiogenesis in rats with diabetic retinopathy(DR)by regulating the interleukin-33/suppression of tumorigenicity 2(IL-33/ST2)signaling pathway.Methods Fifty rats were randomly divided into Col group,DR group,si-circ-NC group,si-circ-001209 group,and si-circ-001209+IL-33 group,with 10 rats in each group.The levels of fasting plasma glucose(FPG)and fasting insulin(FINS)in rats were detected;fundus fluorescein angiography(FFA)was used to detect retinal angiogenesis;the enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of angiogenesis-related factors and inflammatory factors in serum;the hematoxylin-eosin(HE)staining was used to detect histopathological changes in the retina;the periodic acid-Schiff(PAS)staining was used to detect the number of retinal microvascular formations;the Western blotting was used to detect the protein expression levels of IL-33,ST2,vascular endothelial growth factor(VEGF),hypoxia-inducible factor-1α(HIF-1α),and intercellular adhesion molecule-1(ICAM-1)in retinal tissues.Results Compared with the Col group,the DR group and si-circ-NC group showed significant increase in levels of FPG,FINS,serum VEGF,angiopoietin-1(Ang-1),IL-6,IL-33,tumor necrosis factor-α(TNF-α),the number of microvascular formation,and the protein expression levels of IL-33,ST2,VEGF,HIF-1α,and ICAM-1 in retinal tissues(P<0.05);the si-circ-001209 group showed significant decrease in levels of FPG,FINS,serum VEGF,Ang-1,IL-6,IL-33,TNF-α,the number of microvascular formation,and the protein expression levels of IL-33,ST2,VEGF,HIF-1α,and ICAM-1 in retinal tissues compared with the si-circ-NC group(P<0.05);the si-circ-001209+IL-33 group showed significant increase in levels of FPG,FINS,serum VEGF,Ang-1,IL-6,IL-33,TNF-α,the number of microvascular formations,and the protein expression levels of IL-33,ST2,VEGF,HIF-1α,and ICAM-1 in retinal tissues compared with the si-circ-001209 group(P<0.05).Conclusion Knockdown of circ-001209 can inhibit

关 键 词：环状RNA 糖尿病视网膜病变 微血管生成 白细胞介素-33 生长刺激表达基因2蛋白 信号通路 

分 类 号：R587.2[医药卫生—内分泌] R322.1[医药卫生—内科学] Q522[医药卫生—临床医学]