CTRP9通过调节M1/M2巨噬细胞极化改善大鼠心肌梗死后早期心功能的临床研究

Clinical study of CTRP9 improving early cardiac function after myocardial infarction by regulating M1/M2 macrophage polarization in rats

目的探讨C1q/肿瘤坏死因子相关蛋白9(CTRP9)通过调节M1/M2巨噬细胞极化对大鼠心肌梗死后早期心功能的改善作用。方法将SD大鼠60只随机分为对照组、模型组、干预组,每组20只。采用结扎左冠脉前降支方法制作模型组、干预组的心肌梗死大鼠模型,干预组采用pcDNA3.1-CTRP9重组质粒进行干预,比较各组一般情况、心肌梗死面积、心功能[左心射血分数(LVEF)、左心室舒张末期内径(LVDd)、心室收缩末期内径(LVDs)、短轴缩短率(FS)]、心肌细胞凋亡率、M1/M2巨噬细胞极化情况[M1型巨噬细胞F4/80阳性和诱导型一氧化氮合酶(iNOS)阳性百分比、M2型巨噬细胞F4/80阳性和精氨酸酶1(ARG-1)阳性百分比]、心肌组织中CTRP9蛋白表达量。结果干预组大鼠精神状态、毛发生长、饮食活动、存活等一般情况较模型组好转。模型组和干预组心肌细胞凋亡率、心肌梗死面积、LVDs、LVDd、M1型巨噬细胞F4/80阳性和iNOS阳性百分比高于对照组(P<0.05)。干预组心肌细胞凋亡率、心肌梗死面积、LVDs、LVDd、M1型巨噬细胞F4/80阳性和iNOS阳性百分比显著低于模型组(P<0.05)。模型组和干预组LVEF、FS、M2型巨噬细胞F4/80阳性和ARG-1阳性百分比低于对照组(P<0.05)。干预组LVEF、FS、M2型巨噬细胞F4/80阳性和ARG-1阳性百分比高于模型组(P<0.05)。模型组心肌组织中CTRP9蛋白表达量低于对照组(P<0.05),干预组心肌组织中CTRP9蛋白表达量高于模型组和对照组(P<0.05)。结论CTRP9可通过促进M1/M2巨噬细胞极化改善心肌梗死后早期心功能。

Objective To investigate the mechanism of Clq-tumor necrosis factor-related protein-9(CTRP9)improving early cardiac function after myocardial infarction by regulating M1/M2 macrophage polarization in rats.MethodssSixty SD rats were randomly divided into control group,model group and intervention group,with 20 rats in each group.Rats in the model group and the intervention group were made into myocardial infarction model by ligating the left anterior descending coronary artery,and the intervention group received peDNA3.1-CTRP99 recombinantplasmid intervention.Then various indexes were compared among groups,including general condition,myocardial infarction area,cardiac function[left ventricular ejection fraction(LVEF),left ventricular end diastolic diameter(LVDd),left ventricular end-systolic dimension(LVDs),functional shortaxial shortening rate(FS)],cardiomyocyte apoptosis rate,M1/M2 macrophage polarization[M1 type macrophages F4/80 positive and inducible nitric oxide synthase(iNOS)positive percentage,M2 type macrophages F4/80 positive and arginase 1(ARG-1)positive percentage],and protein expression of CTRP9 in myocardial tissue.Results The mental state,hair growth,dietary activity,and survival of rats in intervention group were better than those in model group.The myocardial cell apoptosis rate,myocardial infarction area,LVDs,LVDd,Ml type macrophage F4/80 positive and iNOS positive percentage in model group and intervention group were higher than those in control group(P<0.05).The myocardial cell apoptosis rate,myocardial infarction area,LVDs,LVDd and M1 type macrophages F4/80 positive and iNOS positive percentage in intervention group were significantly lower than those in model group(P<0.05).The percentage of LVEF,FS and M2 type macrophages F4/80 positive and ARG-1 positive percentage in model group and intervention group was lower than those in control group(P<0.05).The LVEF,FS and M2 type macrophages F4/80 positive and ARG-1 positive percentage in the intervention group was higher than that in the model group(P<0.05).The expression of CTRP9 protein in myocardium of the model group was lower than that of the control group(P<0.05),and the expression of CTRP9 protein in myocardium of the intervention group was higher than that of the model group and the control group(P<0.05).Conclusions CTRP9 can improve the early cardiac function after myocardial infarction by promoting the polarization of M1/M2 macrophages.