Effect of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on ischemia-reperfusion injury in rats

被引:33
|
作者
Cao, Zeling
Ye, Ping [1 ]
Long, Chaoliang
Chen, Kai
Li, Xiaowei
Wang, Hai
机构
[1] Chinese Peoples Liberat Army Gen Hosp, Dept Geriatr Cardiol, Beijing 100853, Peoples R China
[2] Beijing Inst Pharmacol & Toxicol, Dept Cardiovasc Pharmacol, Beijing, Peoples R China
关键词
ischemia; reperfusion injury; apoptosis; peroxisome proliferator-activated receptor gamma agonist;
D O I
10.1159/000100870
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Two groups of rats were used to examine the effect of pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, on rat hearts using an in vivo model of ischemia-reperfusion (I/R) to elucidate potential mechanisms. One group was the 30-min reperfusion group, which was further subdivided into sham (n = 5), vehicle ( n = 6) and pioglitazone ( 3 mg (.) kg(-1), n = 7) treatment groups with 30 min ischemia followed by 30 min reperfusion to detect data related to cardiac function and the area of myocardial infarction. The other group was the 120-min reperfusion group, subdivided into sham ( n = 5), vehicle ( n = 6), and pioglitazone 0.3 mg (.) kg - 1 ( n = 6), 1 mg (.) kg - 1 ( n = 7) and 3 mg (.) kg - 1 ( n = 6) treatment groups. Immunohistochemistry, in situ hybridization, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling ( TUNEL) and DNA agarose gel electrophoresis were performed to detect apoptosis and expressions of Bax, Bcl-2, caspase 3, MMP-2 and PPAR gamma protein, and MMP-2 and PPAR gamma mRNA. We found that, after acute treatment with pioglitazone, the ratio of necrosis to area at risk decreased by 28% ( p < 0.01) and that of necrosisto left ventricle was reduced by 32% ( p < 0.01), compared with the vehicle group. Heart rate and + dp/dt(max), representing the cardiac systolic function, as well as -dp/dt(max), the indicator of cardiac diastolic function, improved significantly at 1 and 30 min after reperfusion ( p < 0.05 - 0.01). Furthermore, myocardial apoptosis was significantly suppressed by acute treatment with pioglitazone as evidenced by the decreased number of TUNEL-positive myocytes and DNA ladder, enhanced Bcl-2 protein expression, reduced Bax and caspase 3 protein expression in a dose-dependent manner compared with vehicle-treated rats. In addition, acute treatment with pioglitazone dose-dependently increased PPAR gamma expression and decreased MMP-2 expression at protein and mRNA levels. Our findings demonstrate that a PPAR gamma agonist may protect the heart from I/R injury. The protective effect is likely to occur by reducing cardiomyocyte apoptosis and inhibiting MMP-2. Copyright (c) 2007 S. Karger AG, Basel
引用
收藏
页码:184 / 192
页数:9
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