VEGF对小鼠急性心肌梗死后心肌细胞缺血损伤的保护作用

Protective effect of vascular endothelial growth factor on myocardial ischemic injury after acute myocardial infarction in mice

目的探讨血管内皮生长因子(VEGF)对急性心肌梗死后小鼠心肌细胞缺血损伤的保护作用。方法选取48只成年雄性C57BL/6J小鼠,随机分成三组:假手术组、模型组和VEGF治疗组,每组16只。采用TUNEL试剂盒染色检测心肌细胞凋亡,采用实时荧光定量聚合酶链反应(RT-PCR)检测促炎因子肿瘤坏死因子(TNF-α),白细胞介素1p(IL-1p)和白细胞介素6(IL-6)mRNA表达水平,采用Vevo770高分辨率超声成像系统测量左室收缩末期内径(LVDs)、左室舒张末期内径(LVDd)、左室射血分数(LVEF)、短轴缩短率(FS)以及每搏输出量(SV),采用生化分析法检测小鼠血清心肌酶含量。结果与假手术组比较,模型组和VEGF组小鼠LVDD、LVDS、AST、CPK、LDH含量显著升高以及TNF-α、IL-1β和IL-6 mRNA相对表达量均显著升高(P均<0.05),FS、LVEF、SV显著降低(P均<0.05)。与模型组比较,VEGF组LVDd、LVDs、AST、CPK、LDH含量及TNF-α、IL-1Β和IL-6 mRNA相对表达量均显著降低(P均<0.05),FS、LVEF、SV显著升高(P均<0.05)。与假手术组相比,模型组和VEGF组细胞凋亡明显增加,差异有统计学意义(P<0.05)。与模型组相比,VEGF组细胞凋亡明显降低,差异有统计学意义(P<0.05)。结论VEGF对AMI小鼠具有一定的保护作用,其作用机制可能与VEGF能够改善改善小鼠心肌功能、减轻小鼠心肌细胞炎性反应以及减少细胞凋亡有关。

Objective To investigate the protective effect of vascular endothelial growth factor on myocardial ischemic injury after acute myocardial infarction in mice.Methods Forty-eight adult male C57BL/6J mice were randomly divided into three groups:sham operation group(n=16),model group(n=16)and vascular endothelial growth factor treatment group(n=16).Myocardial cell apoptosis was detected by TUNEL kit staining.The expression levels of TNF-alpha,IL-1p and IL-6 were detected by real-time fluorescence quantitative polymerase chain reaction(RT-PCR).Left ventricle end-systolic diameter(LVDs),left ventricular end-diastolic diameter(LVDd),left ventricular ejection fraction(LVEF),short axis shortening rate(FS),and stroke output(SV)were measured by Vevo770 high resolution ultrasound imaging system.The serum myocardial enzymes were detected by biochemical analysis.Results Compared with sham-operated group,the LVDd,LVDs,AST,CPK and LDH contents,the relative expressions of TNF-alpha,IL-1beta and IL-6 mRNA in model group and VEGF group increased significantly,while FS,LVEF and SV decreased significantly(all P<0.05).Compared with the model group,the levels of LVDd,LVDs,AST,CPK and LDH,the relative expressions of TNF-alpha,IL-1 and IL-6 mRNA in the vascular endothelial growth factor group decreased significantly,while the levels of FS,LVEF and SV increased significantly(all P<0.05).Compared with sham-operated group,apoptosis in model group and vascular endothelial growth factor group increased significantly(P<0.05).Compared with the model group,apoptosis in the vascular endothelial growth factor group was significantly lower(P<0.05).Conclusion The protective effect of vascular endothelial growth factor on AMI mice may be related to the improvement of myocardial function,the alleviation of inflammatory response of myocardial cells and the reduction of apoptosis.