Cilostazol protects the heart against ischaemia reperfusion injury in a rabbit model of myocardial infarction: Focus on adenosine, nitric oxide and mitochondrial ATP-sensitive potassium channels
Cilostazol protects the heart against ischaemia reperfusion injury in a rabbit model of myocardial infarction: Focus on adenosine, nitric oxide and mitochondrial ATP-sensitive potassium channels
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DOI：
10.1111/j.1440-1681.2011.05550.x
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发表时间：
2011-10-01
影响因子：
2.9
通讯作者：
Minatoguchi, Shinya
中科院分区：
文献类型：
--
作者：
Bai, Yushan;Muqier;Minatoguchi, Shinya
1.本研究采用家兔心肌梗死模型，观察西洛他唑是否能缩小心肌梗死范围，并探讨其作用机制.日本白色家兔进行30分钟的冠状动脉闭塞，然后再灌注48小时。缺血前5分钟静脉给予西洛他唑（1和5 mg/kg）或溶媒。在西洛他唑注射前5分钟静脉内给予8-对磺苯基茶碱（8 SPT;腺苷受体阻断剂，7.5 mg/kg）、N ω-硝基-L-精氨酸甲酯（L-NAME; NOS抑制剂，10 mg/kg）或5-羟基癸酸钠盐（5-HD;线粒体ATP敏感性钾（KATP）通道阻断剂，5 mg/kg）。肿瘤大小以占危险区的百分比来确定。测定缺血和再灌注时心肌间质腺苷和一氧化氮（NOx）水平，以及心肌二氢乙锭染色强度.与对照组（46.5%（4.2%））相比，西洛他唑1 mg/kg组（38.4%（2.9%））和西洛他唑5 mg/kg组（30.7%（4.7%））的大鼠睾丸体积显著减小。西洛他唑的缩小梗死面积作用被8 SPT（46.6%（3.5%））、L-NAME（49.0%（5.5%））和5 HD（48.5%（5.1%））完全消除。单用8 SPT、L-NAME或5 HD均不影响梗死范围。西洛他唑治疗显著增加缺血期间心肌腺苷和NOx的水平，并减弱再灌注期间二氢乙锭染色的强度。这些发现表明，西洛他唑通过增加腺苷和NOx水平、减弱超氧化物产生和打开线粒体KATP通道来减小心肌梗死面积。西洛他唑可能为冠心病的治疗提供一种新的策略。
1. The present study examined whether or not cilostazol reduces the myocardial infarct size, and investigated its mechanism in a rabbit model of myocardial infarction.2. Japanese white rabbits underwent 30 min of coronary occlusion, followed by 48 h of reperfusion. Cilostazol (1 and 5 mg/kg) or vehicle was given intravenously 5 min before ischaemia. 8-p-sulfophenyl theophylline (8SPT; an adenosine receptor blocker, 7.5 mg/kg), N omega-nitro-L-arginine methylester (L-NAME; an NOS inhibitor, 10 mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD; a mitochondrial ATP-sensitive potassium (KATP) channel blocker, 5 mg/kg) was given intravenously 5 min before cilostazol injection. Infarct size was determined as a percentage of the risk area.3. The myocardial interstitial levels of adenosine and nitrogen oxide (NOx) during ischaemia and reperfusion, and the intensity of myocardial dihydroethidium staining were determined.4. Infarct size was significantly reduced in the cilostazol 1 mg/kg (38.4% (2.9%)) and cilostazol 5 mg/kg (30.7% (4.7%)) groups compared with that in the control group (46.5% (4.2%)). The infarct size-reducing effect of cilostazol was completely abolished by 8SPT (46.6% (3.5%)), L-NAME (49.0% (5.5%)), or 5HD (48.5% (5.1%)). 8SPT, L-NAME or 5HD alone did not affect the infarct size. Cilostazol treatment significantly increased myocardial levels of adenosine and NOx during ischaemia, and attenuated the intensity of dihydroethidium staining during reperfusion.5. These findings show that cilostazol reduces the myocardial infarct size by increasing adenosine and NOx levels, attenuating superoxide production and opening the mitochondrial KATP channels. Cilostazol might provide a new strategy for the treatment of coronary heart disease.