- 作者：Fan Rong ; Zhang Peng ; Ye Ming-Xiang ; Quan-Yu Zhang ; Yin Zhao ; Shu-Miao Zhang ; Hai-Tao Guo ; Hui Bi ; Yue-Min Wang ; Cheng Liang ; Chun-Hu Gu ; Chen Tao ; Qin Cui ; Shi-Qiang Yu ; Ding-Hua Yi ; Jian-Ming Pei
- 关键词：Ischemia/reperfusion ; κ ; -Opioid receptor ; U50488H ; Apoptosis
- 刊名：Archives of Medical Research
- 出版年：2009
- 出版时间：May 2009
- 年：2009
- 卷：40
- 期：4
- 页码：227-234
- 全文大小：460 K
Background and Aims
It remains unclear whether U50488H (a selective κ-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 45 min coronary artery occlusion and 180 min of reperfusion. U50488H (1.5 mg/kg IV) was given prior to occlusion. Nor-Binaltorphimine (nor-BNI) (2 mg/kg IV), a selective κ-opioid receptor antagonist, was given 10 min 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 kATP 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 κ-opioid receptor may mediate a role in U50488H-induced myocardial protection.