吡格列酮对急性心肌梗死左室功能和心肌细胞凋亡的影响

Effect of Pioglitazone on left ventricular function and cardiomyocytes apoptosis after acute myocardial infarction in mice

目的:观察盐酸吡格列酮对急性心肌梗死(AMI)小鼠左室功能与心肌细胞凋亡的影响,研究调节心肌组织过氧化物酶体增殖物激活受体γ(PPARγ)表达对小鼠心肌梗死的作用。方法:结扎C57BL/6小鼠左冠状动脉制作AMI模型,分为非吡格列酮治疗组(非治疗组)和吡格列酮(20mg.kg-1.d-1)治疗组(治疗组),以假手术组作为对照组。HE染色检测组织病理学改变,TTC染色检测梗死面积,脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)检测心肌细胞凋亡,Western blot检测PPARγ的表达,观察吡格列酮对上述指标的影响。结果:①经吡格列酮治疗14d后,治疗组小鼠病理组织学改变较非治疗组明显减轻,但心肌梗死面积无显著改变[(32.20±4.59)%∶(33.49±5.38)%,P>0.05]。②与假手术组比较,非治疗组左室舒张末期内径(LVEDD)、左室收缩末内径(LVESD)明显升高(P<0.01),左室射血分数(LVEF)、短轴缩短率(FS)明显降低(P<0.01);与非治疗组比较,治疗组LVEDD、LVESD明显升高(P<0.01),LVEF、FS明显降低(P<0.01),但仍高于假手术组(P<0.01)。③与假手术组比较,小鼠心肌梗死后心肌组织TUNEL阳性细胞率明显增加(P<0.01),经吡格列酮治疗14d后明显减少(P<0.01)。④非治疗组小鼠心肌PPARγ蛋白表达高于假手术组,经吡格列酮治疗14d后蛋白表达量显著增加(P<0.01)。结论:吡格列酮能有效降低小鼠心肌梗死后心肌细胞凋亡,改善左室功能。

Objective：To observe the effect of Pioglitazone on the histological change, the apoptosis level of cardiomyocytes and peroxisome proliferator-activated receptor γ （PPARγ） expression after myocardial infarction （MI） in mice in vivo. Method：MI model of mice was established by ligation of the left coronary artery. MI mice were divided into two groups： AMIA group （without any treatment） and AMIB group （treated with Pioglitazone 20 mg . kg 1 . d 1 ）. The mice in sham group underwent the same procedures but without ligating the LAD arte y. The infarct size was assessed by TTC staining and the changes of the cardiac structure after infarction was assessed by HE stain. Left ventricular end-diastolic dimension （LVEDD）, left ventricular end-systolic dimension （LVESD）, fractional shortening （FS）and left ventricular ejection faction （LVEF） were measured with echocardiography. The apoptosis level was examined with dT-mediated dUTP nick end labeling （TUNEL）. The expression of PPARγ protein was examined by Western blot. Result： （1）Fourteen days after treated by Pioglitazone, the myocardial pathology was improved significantly, but infarct size was not changed compared with AMIA group [（32.20 ±4. 59）% vs （33.49±5.38）%, P〉0.05]. （2）Compared with the sham group, LVEDD and LVESD in the AMIA group were reduced greatly （P〈0.01）, FS and LVEF were increased （P〈0.01）. Fourteen days after treated with Pioglitazone, LVEDD and LVESD in AMIB group were significantly increased, FS and LVEF were decreased （P〈0.01） compared with AMIA group. （3）Compared with the sham group, the TUNEL-positive cell percentage in AMIA group was increased. Compared with the AMIA group, the TUNEL-positive cell percentage in the AMIB group was decreased significantly （P〈0.01）. （4）Fourteen days after treated with Pioglitazone, the expression of PPARy was increased obviously in the AMIB group compared with the AMIA group and the sham group （P〈0. 01）. Conclusion：Pioglitazone can improve left ventricular function and cardiomyocytes apoptosis of MI in mice.