摘要
BACKGROUND： Recent studies have suggested that mitochondrial ATP-sensitive K＋ channel openers could reduce myocardium infarct size, and protect the function of the mitochondria. OBJECTIVE： To investigate the changes of cerebral infarction volume and the activity of marker enzymes in brain mitochondria of rats given the ATP-sensitive K＋ channel opener, nicorandil, before focal cerebral ischemia/reperfusion （I/R）. DESIGN, TIME AND SETTING： Randomized, controlled animal experiment, completed at the Brain Scientific Research Center of the Affiliated Hospital of Qingdao University from July to November 2007. MATERIALS： Sixty healthy male Wistar rats weighing 280-300 g. Nicorandil, 5-hydroxydecanoate （5-HD） and cytochrome C were purchased from Sigma in the USA. Standard malondialdehyde （MDA） and protein were purchased from Nanjing Jiancheng Biotechnology Institute. METHODS： Sixty rats were randomly divided into a sham operation group, a middle cerebral artery occlusion （MCAO） group, a nicorandil group and a nicorandil＋5-HD group. MCAO for 2 hours was performed in the MCAO group, nicorandil group and nicorandil＋5-HD group. A total of 5 mL saline were given to the MCAO group before MCAO. The nicorandil group was injected with the ATP-sensitive K＋ channel opener nicorandil 10 mg/kg intraperitoneally 30 minutes before MCAO. The nicorandil＋5-HD group was injected with 5-HD 10 mg/kg intravenously 15 minutes before the same treatment as the nicorandil group. MAIN OUTCOME MEASURES： Infarct volume by total brain slice calculation, activities of succinate dehydrogenase （SDH） and cytochrome oxidase （CO）, and content of MDA were observed at 22 hours of reperfusion after 2 hours MCAO. RESULTS： Sixty rats were included in the final analysis, without any loss. （1） Infarct volume： compared with the MCAO group and nicorandil＋5-HD group, the percentage of infarct volume was significantly decreased in the nicorandil group （P 〈 0.01）. （2） The content of MDA, expression of SDH and CO in brain： the expressions of SDH and CO in the sham operation group were significantly lower than those in the MCAO, nicorandil and nicorandil＋5-HD groups （P 〈 0.01）. The expressions of SDH and CO in the nicorandil group were significantly higher than those in the MCAO and nicorandil＋5-HD groups （P 〈 0.05）. The content of MDA in the brain of the nicorandil group was significantly lower than those in the MCAO and nicorandil＋5-HD groups （P 〈 0.01）. CONCLUSION： Nicorandil can significantly reduce the infarct volume in a rat MCAO model, increase the activity of the mitochondria and protect against cerebral I/R injury.
BACKGROUND： Recent studies have suggested that mitochondrial ATP-sensitive K＋ channel openers could reduce myocardium infarct size, and protect the function of the mitochondria. OBJECTIVE： To investigate the changes of cerebral infarction volume and the activity of marker enzymes in brain mitochondria of rats given the ATP-sensitive K＋ channel opener, nicorandil, before focal cerebral ischemia/reperfusion （I/R）. DESIGN, TIME AND SETTING： Randomized, controlled animal experiment, completed at the Brain Scientific Research Center of the Affiliated Hospital of Qingdao University from July to November 2007. MATERIALS： Sixty healthy male Wistar rats weighing 280-300 g. Nicorandil, 5-hydroxydecanoate （5-HD） and cytochrome C were purchased from Sigma in the USA. Standard malondialdehyde （MDA） and protein were purchased from Nanjing Jiancheng Biotechnology Institute. METHODS： Sixty rats were randomly divided into a sham operation group, a middle cerebral artery occlusion （MCAO） group, a nicorandil group and a nicorandil＋5-HD group. MCAO for 2 hours was performed in the MCAO group, nicorandil group and nicorandil＋5-HD group. A total of 5 mL saline were given to the MCAO group before MCAO. The nicorandil group was injected with the ATP-sensitive K＋ channel opener nicorandil 10 mg/kg intraperitoneally 30 minutes before MCAO. The nicorandil＋5-HD group was injected with 5-HD 10 mg/kg intravenously 15 minutes before the same treatment as the nicorandil group. MAIN OUTCOME MEASURES： Infarct volume by total brain slice calculation, activities of succinate dehydrogenase （SDH） and cytochrome oxidase （CO）, and content of MDA were observed at 22 hours of reperfusion after 2 hours MCAO. RESULTS： Sixty rats were included in the final analysis, without any loss. （1） Infarct volume： compared with the MCAO group and nicorandil＋5-HD group, the percentage of infarct volume was significantly decreased in the nicorandil group （P 〈 0.01）. （2） The content of MDA, expression of SDH and CO in brain： the expressions of SDH and CO in the sham operation group were significantly lower than those in the MCAO, nicorandil and nicorandil＋5-HD groups （P 〈 0.01）. The expressions of SDH and CO in the nicorandil group were significantly higher than those in the MCAO and nicorandil＋5-HD groups （P 〈 0.05）. The content of MDA in the brain of the nicorandil group was significantly lower than those in the MCAO and nicorandil＋5-HD groups （P 〈 0.01）. CONCLUSION： Nicorandil can significantly reduce the infarct volume in a rat MCAO model, increase the activity of the mitochondria and protect against cerebral I/R injury.
