摘要
目的 研究基于PI3K/AKT/GSK3β信号通路研究下调miR-208a对急性心肌梗死模型大鼠的干预作用。方法 选取健康、清洁级SD雄性大鼠40只,建立急性心肌梗死模型,成功37只,其中10只为假手术组,其余为模型组、空白组、miR-208a转染组,每组9只。实时荧光定量PCR检测miR-208a表达,检测心功能相关指标[左心室舒张末期内径(LVDd)、左心室射血分数(LVEF)、左心室收缩末期内径(LVDs)、左心室缩短分数(LVFS)],观察心肌梗死面积、病理组织,检测活性氧(ROS)、转化生长因子β(TGF-β)水平,免疫印迹Western blot检测PI3K、AKT、GSK3β蛋白表达。结果 miR-208a转染组miR-208a表达低于模型组、空白组,高于假手术组(P<0.05);miR-208a转染组LVEF、LVFS高于模型组、空白组,低于假手术组;LVDd、LVDs低于模型组、空白组,高于假手术组(P<0.05);miR-208a转染组心肌梗死面积低于模型组、空白组(P<0.05);miR-208a转染组ROS、TGF-β水平,PI3K、AKT、GSK3β表达低于模型组、空白组,高于假手术组(P<0.05)。结论 下调miR-208a可以抑制PI3K/Akt/GSK3β信号通路相关蛋白,进而抑制心肌细胞凋亡,缓解机体炎性反应,保护机体心肌细胞,最终减缓心肌损伤程度,同时也能改善急性心肌梗死模型大鼠心功能,减少心肌梗死面积,为临床急性心肌梗死靶向治疗提供依据。
Objective To investigate the intervention effects of miR-208a downregulation in rats with acute myocardial infarction(AMI) based on PI3K/AKT/GSK3β signaling pathway.Methods Forty healthy and clean grade male SD rats were enrolled in the study, and the animal models with AMI were established, and the models were successfully established in 37 rats, of whom, 10 rats were in sham operation group, and the rest ones were in model group, blank group and miR-208a transfection group, with 9 rats in each group.Real time fluorescent quantitative PCR was used to detect the expression levels of mir-208a, and the indexes related to cardiac function [left ventricular end diastolic diameter(LVDD),left ventricular ejection fraction(LVEF),left ventricular end systolic diameter(LVDS),left ventricular shortening fraction(lvfs)] were detected, and the infarct size, pathological tissue, reactive oxygen species(ROS),transforming growth factor-β(TGF-β) levels were observed.Moreover the expression levels of PI3K,AKT,GSK3βprotein were detected by Western Blot.Results The expression levels of miR-208a in miR-208a transfection group were significantly lower than those in model group and blank group, however, which were significantly higher than those in sham operation group(P<0.05). The levels of LVEF,LVFS in miR-208a transfection group were significantly higher than those in model group and blank group, however, which were significantly lower than those in sham operation group, and the levels of LVDd and LVDs were significantly lower than those in model and blank group, however, which were significantly higher than those in sham operation group(P<0.05).In addition the MI area in miR-208a transfection group was significantly less than that in model group and blank group(P<0.05).In addition the levels of ROS and TGF-β,PI3K,and the expression levels of AKT,GSK3βin miR-208a transfection group were significantly lower than those in model group and blank group, however, which were significantly higher than those in sham operation group(P<0.05).Conclusion Downregulation of miR-208a can inhibit PI3K/Akt/GSK3β signaling related proteins, so as to inhibit the cardiomyocyte apoptosis, alleviate the body inflammatory response, protect the body cardiomyocytes, eventually slow down the myocardial damage degree, moreover, which can improve the cardiac function of rats with AMI,decrease the myocardial infarction area, which provides the basis for clinical targeted treatment of AMI.
作者
黄晶
雷玉华
华晓芳
周慧
朱贤林
HUANG Jing;LEI Yuhua;HUA Xiaofang(Cardiovascular Diseases Center,Department of Internal Medicine,Central Hospital of Hubei Enshi Tujia Autonomous Prefecture,Hubei,Enshi 445000,China)
出处
《河北医药》
CAS
2022年第23期3530-3533,3537,共5页
Hebei Medical Journal
基金
国家自然科学基金项目(编号:81760257)。
