摘要
目的探究右美托咪定(DEX)对糖尿病心肌缺血/再灌注(MI/R)大鼠心肌损伤及炎性反应的影响和机制。方法将大鼠分为假手术(sham)组、模型(model)组[高脂高糖喂养联合注射链脲佐菌素复制2型糖尿病(T2DM)模型,再结扎冠状动脉复制MI/R损伤模型]、DEX组(T2DM模型大鼠尾静脉注射10μg/kg DEX)、antagomir NC组(T2DM模型大鼠尾静脉注射10μg/kg DEX和antagomir NC)和miR-490-3p antagomir组(T2DM模型大鼠尾静脉注射10μg/kg DEX和miR-490-3p antagomir)。RT-qPCR检测miR-490-3p和叉头框蛋白O1(FOXO1)mRNA的表达;血糖仪测量大鼠空腹血糖(FBG);ELISA测定空腹胰岛素(FINS)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、炎性因子白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的水平;HE染色观察心肌组织病理损伤;TTC染色测定心肌梗死面积;双荧光素酶报告基因实验验证miR-490-3p与FOXO1关系;Western blot检测心肌组织中FOXO1蛋白表达。结果与假手术组比较,模型组FBG、FINS、CK-MB、LDH、IL-1β、TNF-α、心肌梗死面积、FOXO1 mRNA及蛋白表达升高,miR-490-3p表达降低(P<0.05);与模型组比较,DEX组大鼠FBG、FINS、CK-MB、LDH、IL-1β、TNF-α、心肌梗死面积、FOXO1 mRNA及蛋白表达降低,miR-490-3p表达升高(P<0.05);下调miR-490-3p可明显减弱DEX对模型组大鼠心肌损伤及炎性反应的改善作用(P<0.05);FOXO1与miR-490-3p存在靶向调控关系。结论DEX可能通过调节miR-490-3p/FOXO1轴,抑制炎性反应,减轻糖尿病模型大鼠MI/R引起的心肌损伤。
Objective To explore the effect and mechanism of dexmedetomidine(DEX)on myocardial injury and inflammation of rats with diabetic myocardial ischemia-reperfusion(MI/R).Methods The rats were divided into sham group,model grousp[The type 2 diabetes mellitus(T2DM)model was replicated by feeding high-fat and high-sugar combined with streptozotocin injection;MI/R injury model was replicated by coronary artery ligation],DEX group(T2DM model rats were injected with 10μg/kg DEX through tail vein),antagomir NC group(T2DM model rats were injected with 10μg/kg DEX and antagomir NC through tail vein),miR-490-3p antagomir group(T2DM model rats were injected with 10μg/kg DEX and miR-490-3p antagomir via tail vein).RT-qPCR was applied to detect the expression of miR-490-3p and forkhead box O1(FOXO1)mRNA;Blood glucose meter was applied to measure fasting blood glucose(FBG)in rats;The level of fasting insulin(FINS),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH)and inflammatory factors interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)was measured by ELISA;HE staining microscopy was applied to observe pathological damage of myocardial tissue;TTC staining microscopy was applied to determine the size of myocardial infarction;Dual luciferase assay was applied to verify the relationship between miR-490-3p and FOXO1;Western blot was applied to detect the expression of FOXO1 protein in myocardial tissue.Results Compared with the sham group,the FBG,FINS,CK-MB,LDH,IL-1β,TNF-α,myocardial infarction area,FOXO1 mRNA and protein expression in model group were all increased,while miR-490-3p expression decreased(P<0.05);Compared with the model group,the FBG,FINS,CK-MB,LDH,IL-1β,TNF-α,myocardial infarction area,FOXO1 mRNA and protein expression in rats from DEX group decreased,the miR-490-3p expression increased(P<0.05);Down regulation of miR-490-3p was able to significantly baffle the improvement of DEX on myocardial injury and inflammation in diabetes MI/R rats(P<0.05);FOXO1 had a target-specific regulatory relationship with miR-490-3p.Conclusions DEX may inhibit inflammation and alleviate myocardial injury induced by MI/R in diabetic rat models by regulating the miR-490-3p/FOXO1 axis.
作者
刘彬
刘文平
靳涛
LIU Bin;LIU Wenping;JIN Tao(Department of Anesthesiology,Cangzhou Hospital of Integrated Traditional and Western Medicine,Cangzhou 061000,China;Department of Cardiology,Cangzhou Hospital of Integrated Traditional and Western Medicine,Cangzhou 061000,China)
出处
《基础医学与临床》
CAS
2024年第11期1538-1543,共6页
Basic and Clinical Medicine
基金
河北省2022年度医学科学研究课题计划(20220689)。
