罗格列酮对心肌梗死大鼠血流动力学、梗死面积及心肌细胞凋亡的影响

Influence of Rosiglitazone on the Ventricular Haemodynamics,Histological Change,and Apoptosis Level of Cardiomyocytes in Rat's Myocardial Infarction Models

目的:观察马来酸罗格列酮对心肌梗死大鼠血流动力学、梗死面积、心肌细胞凋亡率的影响,研究调节心肌组织过氧化物酶体增殖物激活受体γ(PPARγ)基因表达对大鼠心肌梗死的作用。方法:结扎大鼠左冠状动脉主干制作心肌梗死模型,分为非罗格列酮治疗组(AMIA)和罗格列酮[5mg/(kg.d)]治疗组(AMIB),以假手术组作为对照组,MP-150生理记录仪检测血流动力学变化,HE染色检测梗死面积,流式细胞术检测心肌细胞凋亡率,RT-PCR检测心肌组织PPARγ基因表达,观察罗格列酮对上述指标的影响。结果:①左冠状动脉主干结扎后大鼠心功能下降,与假手术组相比,AMIA组大鼠平均动脉压(MAP)、左室收缩峰压(LVPSP)和左室等容期压力变化的最大速率(±dp/dt max)均明显降低,LVEDP升高[(15.5±2.35)比(4.52±0.57)mmHg,P<0.05].②经罗格列酮治疗14 d后,心梗大鼠左室舒张末期后(LVEDP)较AMIA组明显下降[(10.14±2.28)比(15.5±2.35)mm-Hg,P<0.01],心梗面积减少33%,病理组织学改变较AMIA组明显减轻。③大鼠心肌梗死后心肌细胞凋亡率较假手术组升高21.15倍,经罗格列酮治疗14 d后,心肌细胞凋亡率较AMIA组明显降低[(16.04±2.26)%比(26.44±3.51)%,P<0.01]。④经罗格列酮治疗后,心肌梗死大鼠心肌组织PPARγ基因表达量较AMIA及假手术组明显增加[分别为(2.352±0.159),(1.574±0.196)与(0.491±0.078),P<0.001]。结论:罗格列酮能有效降低大鼠心肌梗死后心肌细胞凋亡,减少心肌梗死面积,这可能与其上调梗死后心肌组织中PPARγ基因表达水平,发挥了PPARγ对心肌细胞及局部血管的保护作用有关。

Objective： To observe the effect of Rosiglitazone maleate on the ventricular haemodynamics, histological change, apoptosis level of cardiomyocytes, and peroxisome proliferator-activated receptorγ （PPARγ） gene expression after myocardial infarction in aged rats. Methods： Acute myocardial infarction （AMI） model of aged rat was established by ligation of the left coronary artery. AMI rats were divided into AMIA group （AMI rats without any treatment） and AMIB group （AMI rats were treated with PPARγagonists Rosiglitazone 5 mg/kg per day）. The rats in sham group underwent the same procedures except ligation of the LAD artery. The infarct size and the changes of the cardiac structure after infarction were assessed by the method of hematoxylin-eosin stain. The cardiac function was evaluated by the physiological signal recording system. The apoptosis level was examined with the method of flow cytometry. The expression of PPARγwas examined by RT PCR. Results： （1）The cardiac function decreased after AMI. Compared with those in the sham group, the mean artery pressure （MAP）, left ventricular peak end-systolic pressure （LVPSP） and dp/dtmax AMIA group were decreased respectively （all P〈0. 05）, but left ventricular end-diastolic pressure （LVEDP） increased significantly （P〈0. 05）. （2）After 14 days of treatment by Rosiglitazone, the LVEDP declined （P〈0.05）, and the infarct size decreased 33% compared with that of AMIA group. The change of the cardiac structure after infarction in AMIB group was better than in AMIA group. （3）AMIA rats＇ apoptosis level was as high as 21.15-fold of that in the sham group. Compared with that in AMIA group, after 14 days treatment by Rosiglitazone, the apoptosis level was decreased significantly （P〈0.05）. （4）Compared with AMIA group and the sham group, expression of PPARγwas increased obviously in AMIB group （both P〈0. 001）. Conclusion： Rosiglitazone can decrease the infarct size and apoptosis level of AMI in rats. The effect of Rosiglitazone may be associated with the increase of PPARγ gene expression, which can protect the function of cardiomyocytes and vessles.