芦丁调控miR-155和HMGB1/RAGE通路对糖尿病视网膜病变大鼠炎性反应的影响  

Effect of rutin on inflammatory response in diabetic retinopathy rats by regulating miR-155 and HMGB1/RAGE pathway

作　　者：王雅清 王勇[1] 刘永胜[1] WANG Yaqing;WANG Yong;LIU Yongsheng(Department of Endocrinology,the No.2 Hospital of Baoding,Baoding 071051,China)

机构地区：[1]保定市第二医院内分泌科,河北保定071051

出　　处：《陕西医学杂志》2024年第2期184-188,共5页Shaanxi Medical Journal

基　　金：河北省卫生健康委员会医学科学研究计划项目(20232040);河北省保定市科学技术研究与发展计划项目(2141ZF008)。

摘　　要：目的:探讨芦丁对糖尿病视网膜病变大鼠炎性反应的影响及其机制。方法:采用腹腔注射链脲佐菌素的方法制备糖尿病大鼠模型,将造模成功的大鼠随机分为模型组(0.9%氯化钠溶液灌胃)和芦丁低、中、高剂量组[分别以50、100、150 mg/(kg·d)芦丁灌胃],并取正常大鼠作为对照组(0.9%氯化钠溶液灌胃),每组20只,持续给药12周后,比较各组大鼠视网膜组织中伊凡斯兰渗透量、神经节细胞凋亡和微小RNA(miR)-155、高迁移率族蛋白1(HMGB1)、晚期糖基化终产物受体(RAGE)mRNA表达水平,以及炎症因子水平。结果:对照组、模型组和芦丁低、中、高剂量组中伊凡斯兰渗透量分别为(1.61±0.31)μg/g、(12.84±1.24)μg/g、(9.85±0.62)μg/g、(6.80±0.53)μg/g、(2.87±0.51)μg/g,神经节细胞凋亡指数分别为(1.09±0.45)%、(30.96±2.50)%、(24.65±2.48)%、(18.61±1.41)%、(8.36±0.54)%,miR-155表达水平分别为(0.38±0.03)、(1.92±0.15)、(1.55±0.12)、(1.09±0.10)、(0.55±0.05),HMGB1 mRNA表达水平分别为(0.26±0.03)、(0.77±0.05)、(0.68±0.04)、(0.57±0.04)、(0.34±0.03),RAGE mRNA表达水平分别为(0.18±0.02)、(0.67±0.04)、(0.58±0.03)、(0.45±0.03)、(0.23±0.02)。模型组和对照组比较,伊凡斯兰渗透量、凋亡指数和miR-155、HMGB1、RAGE mRNA水平均升高(均P<0.05);芦丁低、中、高剂量组中上述指标呈剂量依赖性降低(均P<0.05)。模型组、对照组与芦丁低、中、高剂量组,芦丁各组的炎症因子水平低于模型组(均P<0.05)。结论:芦丁可保护糖尿病大鼠视网膜损伤,延缓视网膜炎症效应,其作用机制可能与抑制miR-155和HMGB1/RAGE通路有关。Objective:To investigate the effect of rutin on inflammatory response in rats with diabetic retinopathy and its mechanism.Methods:The diabetic rat model was established by intraperitoneal injection of streptozotocin.The successful diabetic rats were randomly divided into model group(intragastric administration of 0.9%sodium chloride solution),low-,medium-and high-dose rutin groups(intragastric administration of 50,100,and 150 mg/kg rutin,respectively),and normal rats were taken as control group(intragastric administration of 0.9%sodium chloride solution),with 20 rats in each group.After 12 weeks of continuous administration,the permeability of evans blue,the apoptosis of ganglion cells,the mRNA expression levels of miR-155,HMGB1,RAGE,and the levels of inflammatory factors in the retinal tissue of each group were compared.Results:In control group,model group and low,middle and high-dose rutin groups,the permeability of evans blue,were(1.61±0.31)μg/g,(12.84±1.24)μg/g,(9.85±0.62)μg/g,(6.80±0.53)μg/g,(2.87±0.51)μg/g,respectively;the ganglion cell apoptosis index were(1.09±0.45)%,(30.96±2.50)%,(24.65±2.48)%,(18.61±1.41)%,(8.36±0.54)%,respectively;the expression levels of miR-155 were(0.38±0.03),(1.92±0.15),(1.55±0.12),(1.09±0.10)and(0.55±0.05),respectively;HMGB1 mRNA expression levels were(0.26±0.03),(0.77±0.05),(0.68±0.04),(0.57±0.04),(0.34±0.03),respectively;the mRNA expression level of RAGE were(0.18±0.02),(0.67±0.04),(0.58±0.03),(0.45±0.03)and(0.23±0.02),respectively.Compared with the control group,the permeability of evans blue,apoptosis index and the mRNA levels of miR-155,HMGB1 and RAGE were increased in the model group(all P<0.05),and these parameters were decreased in a dose-dependent manner in the low-,medium-and high-dose rutin groups(all P<0.05).The levels of inflammatory factors in the model group,the control group and the low-,medium-and high-dose rutin groups were lower than those in the model group(all P<0.05).Conclusion:Rut can protect retinal damage and delay retinal inf

关 键 词：糖尿病视网膜病变 芦丁 微小RNA-155 高迁移率族蛋白1 晚期糖基化终产物受体 炎性反应 

分 类 号：R774[医药卫生—眼科]