PPARγ1基因转染对心肌缺血再灌注后的影响和意义

Effect of myocardial PPARγ1 gene transfection in rat after myocardial ischemia reperfusion injury

摘要:

目的  探讨心肌细胞过表达过氧化物酶体增殖物激活受体γ1（PPARγ1）基因后对缺血再灌注损伤导致的血流动力学、心肌梗死（心梗）面积、血清肌钙蛋白I（cTnI）及心肌基质金属蛋白酶-9（MMP-9）浓度的变化及意义。方法  30只SD大鼠随机分成3组（n =10）：SHAM组、MIRI组及PPARγ1组。SHAM组和MIRI组开胸经冠状动脉（冠脉）转染携带绿色荧光蛋白的腺病毒载体（Ad-EGFP），PPARγ1组转染携带PPARγ1基因的腺病毒载体（Ad-PPARγ1）至心肌组织。稳定3 d后重新开胸，SHAM组只过线，不接扎；MIRI组及PPARγ1组结扎冠脉左前降支30 min，再灌注120 min。观察缺血前（T0）、缺血30 min（T1）、再灌注30 min（T2）、再灌注120 min（T3）时的心率（HR）、平均动脉压（MAP）、左室收缩压（LVSP）、左室舒张末压（LVEDP），左室压最大上升和下降速率（±dp/dt max）；再灌注120 min时检测心梗面积、血清心肌肌钙蛋白I（cTnI）和组织MMP-9浓度的变化。结果  与T0时比较，T1～T3时MIRI组、PPARγ1组LVEDP升高，HR减慢，LVSP和（±dp/dt max）降低，MAP除PPARγ1组在T3时差异无统计学意义，也明显降低（P <0.05）；与SHAM组比较，T1～T3时MIRI组、PPARγ1组LVEDP升高，HR减慢，LVSP和（±dp/dt max）降低，MAP除PPARγ1组在T3时差异无统计学意义，也明显降低（P <0.05）；与MIRI组比较，PPARγ1组±dp/dt max升高，LVSP在T2、T3时升高，MAP在T3时升高（P <0.05）；SHAM组无心肌梗死，MIRI组和PPARγ1组的缺血面积差异无统计学意义（P >0.05），而MIRI组和PPARγ1组心肌梗死面积、cTnI和MMP-9均高于SHAM组，PPARγ1组低于MIRI组（P <
0.05）。结论  过表达PPARγ1基因能通过减轻缺血再灌注过程中血流动力学紊乱、减少心梗面积、降低血清cTnI及组织MMP-9的浓度，从而起到保护心肌的作用。

Abstract:

Objective To investigate the effects of overexpression of peroxisome proliferator-activated receptor γ1 (PPARγ1) gene in myocardial cells on the changes of hemodynamics, the myocardial infract areas and the concentrations of inserum cTnI and tissue MMP-9 in rats after myocardial ischemia-reperfusion injury. Methods Thirty SD rats were randomly divided into three groups (n = 10): SHAM group, MIRI group and PPARγ1 group. In the SHAM group and the MIRI group, myocardial tissues were transfected with recombinant adenovirus vector encoding enhanced green fluorescent protein (Ad-EGFP) via coronary artery. In PPARγ1 group, myocardial tissues were transfected with recombinant adenovirus vector mediated human PPARγ1 gene (Ad-PPARγ1). Three days after gene transfection, rats were operated for MIRI experiment. In group MIRI and PPARγ1, rats were subjected to 30 min of ischemia induced by ligating the left anterior descending branch (LADB) followed by 120 min of reperfusion. In the SHAM group, the rats only underwent open-chest surgery without ligation on the LADB. The HR, MAP, LVSP, LVEDP and (± dp/dt max) were observed at T0 (before ligation), T1 (ligation after 30 min), T2 (reperfusion after 30 min), T3 (reperfusion after 120 min). The myocardial infract areas, concentrations of cTnI in serum and MMP-9 in myocardial tissue were also assessed at 120 min after reperfusion. Results HR, LVSP, MAP (excepted at T3) and (± dp/dt max) were significantly reduced and LVEDP was increased in the MIRI group and PPARγ1 group compared to T0 (P < 0.05). HR, LVSP, MAP (excepted at T3) and (± dp/dt max) in the MIRI group and PPARγ1 group were significantly decreased compared to the SHAM group (P < 0.05). (± dp/dt max), LVSP at T2 and T3, MAP at T3 in the PPARγ1 group showed a significant increase compared with the MIRI group. There was no myocardial infarction in the SHAM group, and there was no significant difference in the myocardial ischemia area between MIRI group and PPARγ1 group (P > 0.05). The myocardial ischemia areas and the concentration of cTnI in serum and MMP-9 in myocardial tissue in the MIRI group and PPARγ1 group were significantly higher than those of the SHAM group, meanwhile these results in PPARγ1 group were significantly less than the MIRI group (P < 0.05). Conclusions Overexpression of PPARγ1 gene could protect myocardial by improving hemodynamic parameters, decreasing the infarct size and reducing the concentration of cTnI in serum and MMP-9 in tissue when myocardial ischemia-reperfusion injury happens.