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PPAR γ1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
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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(PPAR γ1)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(cTn Ⅰ)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PPAR γ1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),PPAR γ1组转染携带PPAR γ1基因的腺病毒载体(Ad-PPAR γ1)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PPAR γ1组结扎冠脉左前降支30min,再灌注120min。观察缺血前(T_0)、缺血30min(T_1)、再灌注30min(T_2)、再灌注120 min(T_3)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(cTn Ⅰ)和组织MMP-9浓度的变化。结果与T_0时比较,T_1~T_3时MIRI组、PPAR γ1组LVEDP升高,HR减慢,LVSP和(±dp/dt max)降低,MAP除PPAR γ1组在T_3时差异无统计学意义,也明显降低(P<0.05);与SHAM组比较,T_1~T_3时MIRI组、PPAR γ1组LVEDP升高,HR减慢,LVSP和(±dp/dt max)降低,MAP除PPAR γ1组在T_3时差异无统计学意义,也明显降低(P<0.05);与MIRI组比较,PPAR γ1组±dp/dt max升高,LVSP在T_2、T_3时升高,MAP在T_3时升高(P<0.05);SHAM组无心肌梗死,MIRI组和PPAR γ1组的缺血面积差异无统计学意义(P>0.05),而MIRI组和PPAR γ1组心肌梗死面积、cTn Ⅰ和MMP-9均高于SHAM组,PPAR γ1组低于MIRI组(P<0.05)。结论过表达PPAR γ1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cTn Ⅰ及组织MMP-9的浓度,从而起到保护心肌的作用。 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 isehemia-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 recom- binant adenovirus vector encoding enhanced green fluorescent protein (Ad-EGFP) via coronary artery. InPPARγ1 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 30min 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 To (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 To (P〈 0.05). HR, LVSP, MAP (excepted at T3) and (± dp/dt max) in the MIRI group and PPARγ1 group were sig- nificantly 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 betw
出处 《中国现代医学杂志》 CAS 北大核心 2017年第11期20-25,共6页 China Journal of Modern Medicine
基金 湖南省教育厅科研项目(No:16C0971)
关键词 心肌缺血再灌注损伤 过氧化物酶体增殖物激活受体γ1 血流动力学 心肌梗死面积 心肌肌钙蛋白Ⅰ 基质金属蛋白酶-9 myocardial ischemia-reperfusion injury peroxisome proliferator-activated receptorγ1 hemo-dynamic myocardial infarction size cardiac troponin I myocardial matrix metalloproteinase-9
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