BACKGROUND： Brief exposure to the anesthetic sevoflurane results in delayed neuroprotection, However, few studies have addressed delayed neuroprotection after preconditioning with a single administration of sevoflura...BACKGROUND： Brief exposure to the anesthetic sevoflurane results in delayed neuroprotection, However, few studies have addressed delayed neuroprotection after preconditioning with a single administration of sevoflurane. OBJECTIVE： To explore the relationship between a single preconditioning administration of sevoflurane and reactive oxygen species production and protein kinase C-epsilon （PKC-ε ） translocation. DESIGN, TIME, AND SETTING： The randomized, controlled, animal experiment was conducted at the Central Laboratory, Xiangya Hospital, Central South University, China from November 2007 to April 2008. MATERIALS： A total of 120 healthy, male, Sprague Dawley rats were equally and randomly assigned into five groups： sham operation, ischemia/reperfusion, sevoflurane, 2-mercaptopropionylglycine （2-MPG, a selective reactive oxygen species scavenger） ＋ sevoflurane （MPG ＋ sevoflurane）, and MPG. Sevoflurane （Baxter, USA） and MPG （Sigma, USA） were used in this study. METHODS： Intervention consisted of three procedures. （1） MPG injection： a selective reactive oxygen species scavenger, MPG （20 mg/kg）, was infused into the rat caudal vein in the MPG and MPG ＋ sevoflurane groups. （2） Sevoflurane preconditioning： 30 minutes following MPG injection, rats in the sevoflurane and MPG ＋ sevoflurane groups breathed a mixed gas of 2.4% sevoflurane and 97.6% oxygen for 60 minutes. Rats in the sham operation, ischemia/reperfusion, and MPG groups breathed 100% pure oxygen for 60 minutes. （3） IschemiaJreperfusion： 24 hours after sevoflurane or pure oxygen preconditioning, middle cerebral artery occlusion models were established in the ischemia/reperfusion, sevoflurane, MPG ＋ sevoflurane, and MPG groups. Following 2 hours ischemia/6 hours and 24 hours reperfusion, the carotid artery was separated, but the middle cerebral artery was not occluded, in the sham operation group. MAIN OUTCOME MEASURES： In the ischemic hemisphere, PKC-ε translocation in the rat parietal cortex was measured by Western blot analysis. Infarct volume was calculated using the TTC assay. Neurological deficits were evaluated in rats using a scoring system of 8 points. RESULTS： After 6 hours reperfusion, the ratio of PKC-ε in membrane/（cytosol ＋ membrane） was significantly less in the sham operation group than in the ischemia/reperfusion, sevoflurane, MPG ＋ sevoflurane）, and MPG groups （P 〈 0.05）. The ratio of PKC-ε in membrane/（cytosol ＋ membrane） was significantly greater in the sevoflurane group than in the sham operation, ischemia/reperfusion, MPG ＋ sevoflurane, and MPG groups （P 〈 0.05）. No significant differences were observed in the ischemiaJreperfusJon, M PG ＋ sevoflurane, and MPG groups （P 〉 0.05）. Following 24 hours reperfusion, the ratio of PKC-ε in membrane/（cytosol ＋ membrane） was significantly less in the sham operation group than in the ischemia/reperfusion, sevoflurane, MPG ＋ sevoflurane, and MPG groups （P 〈 0.05）. No significant differences were detected in the ischemia/reperfusion, sevoflurane, MPG ＋ sevoflurane, and MPG groups （P 〉 0.05）. Compared with the ischemia/reperfusion, MPG ＋ sevoflurane, and MPG groups, infarct volume was significantly smaller, and neurological deficits were significantly improved, in the sevoflurane group （P 〈 0.05）. No significant differences in infarct volume and neurological deficits were observed among the ischemia/reperfusion, MPG ＋ sevoflurane, and MPG groups （P 〉 0.05）. Infarcts or neurological deficits were not detected in the sham operation group. CONCLUSION： A single preconditioning administration of sevoflurane reduced infarct volumes and improved neurological deficits in ischemic rats. Delayed neuroprotection may be mediated by reactive oxygen species and correlated to PKC- ε activation.展开更多
文摘BACKGROUND： Brief exposure to the anesthetic sevoflurane results in delayed neuroprotection, However, few studies have addressed delayed neuroprotection after preconditioning with a single administration of sevoflurane. OBJECTIVE： To explore the relationship between a single preconditioning administration of sevoflurane and reactive oxygen species production and protein kinase C-epsilon （PKC-ε ） translocation. DESIGN, TIME, AND SETTING： The randomized, controlled, animal experiment was conducted at the Central Laboratory, Xiangya Hospital, Central South University, China from November 2007 to April 2008. MATERIALS： A total of 120 healthy, male, Sprague Dawley rats were equally and randomly assigned into five groups： sham operation, ischemia/reperfusion, sevoflurane, 2-mercaptopropionylglycine （2-MPG, a selective reactive oxygen species scavenger） ＋ sevoflurane （MPG ＋ sevoflurane）, and MPG. Sevoflurane （Baxter, USA） and MPG （Sigma, USA） were used in this study. METHODS： Intervention consisted of three procedures. （1） MPG injection： a selective reactive oxygen species scavenger, MPG （20 mg/kg）, was infused into the rat caudal vein in the MPG and MPG ＋ sevoflurane groups. （2） Sevoflurane preconditioning： 30 minutes following MPG injection, rats in the sevoflurane and MPG ＋ sevoflurane groups breathed a mixed gas of 2.4% sevoflurane and 97.6% oxygen for 60 minutes. Rats in the sham operation, ischemia/reperfusion, and MPG groups breathed 100% pure oxygen for 60 minutes. （3） IschemiaJreperfusion： 24 hours after sevoflurane or pure oxygen preconditioning, middle cerebral artery occlusion models were established in the ischemia/reperfusion, sevoflurane, MPG ＋ sevoflurane, and MPG groups. Following 2 hours ischemia/6 hours and 24 hours reperfusion, the carotid artery was separated, but the middle cerebral artery was not occluded, in the sham operation group. MAIN OUTCOME MEASURES： In the ischemic hemisphere, PKC-ε translocation in the rat parietal cortex was measured by Western blot analysis. Infarct volume was calculated using the TTC assay. Neurological deficits were evaluated in rats using a scoring system of 8 points. RESULTS： After 6 hours reperfusion, the ratio of PKC-ε in membrane/（cytosol ＋ membrane） was significantly less in the sham operation group than in the ischemia/reperfusion, sevoflurane, MPG ＋ sevoflurane）, and MPG groups （P 〈 0.05）. The ratio of PKC-ε in membrane/（cytosol ＋ membrane） was significantly greater in the sevoflurane group than in the sham operation, ischemia/reperfusion, MPG ＋ sevoflurane, and MPG groups （P 〈 0.05）. No significant differences were observed in the ischemiaJreperfusJon, M PG ＋ sevoflurane, and MPG groups （P 〉 0.05）. Following 24 hours reperfusion, the ratio of PKC-ε in membrane/（cytosol ＋ membrane） was significantly less in the sham operation group than in the ischemia/reperfusion, sevoflurane, MPG ＋ sevoflurane, and MPG groups （P 〈 0.05）. No significant differences were detected in the ischemia/reperfusion, sevoflurane, MPG ＋ sevoflurane, and MPG groups （P 〉 0.05）. Compared with the ischemia/reperfusion, MPG ＋ sevoflurane, and MPG groups, infarct volume was significantly smaller, and neurological deficits were significantly improved, in the sevoflurane group （P 〈 0.05）. No significant differences in infarct volume and neurological deficits were observed among the ischemia/reperfusion, MPG ＋ sevoflurane, and MPG groups （P 〉 0.05）. Infarcts or neurological deficits were not detected in the sham operation group. CONCLUSION： A single preconditioning administration of sevoflurane reduced infarct volumes and improved neurological deficits in ischemic rats. Delayed neuroprotection may be mediated by reactive oxygen species and correlated to PKC- ε activation.
