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Myocardial apoptosis and infarction after ischemia/reperfusion are attenuated by kappa-opioid receptor agonist.

Abstract：

BACKGROUND AND AIMS:It remains unclear whether U50488H (a selective kappa-opioid receptor agonist) produces anti-apoptotic effect during ischemia and reperfusion (I/R). Therefore, the effect of U50488H on myocardial apoptosis was investigated in the present study. METHODS:Rats were subjected to 45min coronary artery occlusion and 180min of reperfusion. U50488H (1.5mg/kg IV) was given prior to occlusion. Nor-Binaltorphimine (nor-BNI) (2mg/kg IV), a selective kappa-opioid receptor antagonist, was given 10min prior to U50488H. Cardiac apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay and in situ identification of nuclear DNA fragmentation. RESULTS:The ultrastructure injury of myocardium, myocardial infarct size, and plasma CK and LDH were reduced significantly with administration of U50488H before I/R, whereas the effects of U50488H were abolished by nor-BNI. DNA fragments were visualized by agarose electrophoresis, and clear DNA ladder formation was observed in myocardial tissue from hearts subjected to I/R. Administration of U50488H before ischemia exerted a significant anti-apoptotic effect as evidenced by markedly weaker DNA ladder formation. TUNEL staining showed U50488H treatment before I/R significantly reduced the percentage of apoptotic cells, which was blocked by 5-HD, a mitochondrial k(ATP) channel blocker. In accordance, U50488H treatment significantly inhibited I/R-induced elevated activities of caspase-3 and caspase-9. U50488H also produced an increase in Bcl-2 and a decrease in Bax protein expression in the I/R heart, and the anti-apoptotic effects of U50488H were all blocked by nor-BNI. CONCLUSIONS:U50488H reduces myocardial necrosis and apoptosis after I/R and activation of kappa-opioid receptor may mediate a role in U50488H-induced myocardial protection.

journal_name

Arch Med Res

journal_title

Archives of medical research

authors

Rong F,Peng Z,Ye MX,Zhang QY,Zhao Y,Zhang SM,Guo HT,Hui B,Wang YM,Liang C,Gu CH,Tao C,Cui Q,Yu SQ,Yi DH,Pei JM

doi

10.1016/j.arcmed.2009.04.009

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

227-34

issue

4

eissn

0188-4409

issn

1873-5487

pii

S0188-4409(09)00075-7

journal_volume

40

pub_type

杂志文章

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