激活PPARδ对梗死心肌MMP-9及纤连蛋白表达的影响

Effect of PPARδ activation on expression of MMP-9 and fibronectin in infarcted myocardium

目的:研究过氧化物酶体增殖物激活受体δ(PPARδ)激动剂GW610742X对梗死心肌重塑过程中基质金属蛋白酶9(MMP-9)及细胞间基质纤连蛋白(FN)表达的影响。方法:雄性Wistar大鼠,分为对照组、假手术组、心肌梗死(MI)组和MI+GW610742X(GW)组。结扎大鼠左冠状动脉建立MI模型,GW组予以GW610742X(100mg.kg-1.d-1)喂养。术后3个月检测各组大鼠左心室游离壁(LVFW)中PPARδ、MMP-9及FN的mRNA及蛋白表达;免疫荧光法检测LVFW中FN的分布。结果:MI组术后3个月LVFW心肌有不同程度的坏死及纤维化。MI组PPARδ表达高于对照组、假手术组及GW组(P<0.01),GW组PPARδ表达低于对照组及假手术组(P<0.05);MI组及GW组MMP-9表达高于对照组及假手术组,FN表达低于对照组及假手术组(P<0.01或P<0.05)。GW组MMP-9表达低于MI组(P<0.05),FN表达高于MI组(P<0.01)。假手术组与对照组MMP-9及FN的表达无显著差异(P>0.05)。结论:梗死心肌重构过程中,MMP-9表达上调,FN被降解;激活PPARδ可能通过抑制MMP-9的表达,减轻FN的降解,从而改善心肌重塑。

AIM ： To investigate the effect of peroxisome proliferator - activated receptor 8 （PPARS） activation with dietary GW610742X on the expression of matrix metalloproteinase- 9 （MMP- 9 ） and fibronectin （FN） in infarcted and remodeling myocardium. METHODS ： Wistar rats were divided into 4 groups ： control group, sham group, myocardial infarction （MI） group and MI ＋ GW610742X （GW） group. The left coronary artery was ligated to establish the MI model. PPAR8 activator GW610742X （ 100 mg·kg^-1·d^-1 ） was given to the rats in GW group. At the 3rd month of the procedure, the expression of PPARS, MMP -9 and FN at mRNA and protein levels in the left ventricular free wall（LVFW） of the heart from each group was identified and the distribution of FN was detected by immunofluorescence. RESULTS ： After 3 months following the procedure, obvious necrosis and fibrosis in LVFW were observed in MI group. The expression of PPAR8 in MI group was higher than that in control, sham and GW groups （ P 〈0. 01 ）, and PPAR8 expression in GW group was lower than that in control and sham group （P 〈 0.05）. In MI and GW groups, the expression of MMP - 9 was higher while the expression of FN was lower than those in control and sham group （ P 〈 0.05 or P 〈 0.01 ）. In GW group, the expression of MMP - 9 was lower （ P 〈0. 05 ） while the expression of FN was higher （ P 〈 0. 01 ） than those in MI group. Meanwhile, the expression of MMP - 9 and FN in sham group was similar to those in control group （ P 〉 0.05 ）. CONCLUSION： MMP -9 is upregulated and FN is downregulated in infarcted myocardium during the remodeling process. Activation of PPAR8 inhibits the upregulation of MMP - 9 and degradation of FN, thus ameliorating the myocardial remodeling.