Role of PI3K/Akt signal pathway in sevoflurane postconditioning against focal cerebral ischemia-reperfusion injury in rats

Objective To investigate the role of PI3KIAkt signal pathway in sevoflurane postconditioning against focal cerebral ischemia-reperfusion （I/R） injury. Methods Sixty-four adult male SD rats weighing 300- 350 g were randomly assigned into 4 groups （ n = 16 each） ： group I focal cerebral I/R （group I/R） ; group II sevoflurane postconditioning （group SP） ; group III sevoflurane postconditioning ＋ wortmannin （group SP ＋ W） and group IV I/R ＋ wortmannin （group I/R ＋ W） . The animals were anesthetized with intraperitoneal 10% chloral hydrate 300-350 mg/kg, traeheostomized and mechanically ventilated. ECG was continuously monitored. Right femoral artery was cannulated for BP monitoring. Focal cerebral I/R was induced by electro-coagulation of left middle cerebral artery and 60 min occlusion of bilateral common carotid arteries followed by reperfusion. The animals inhaled 2.5% sevoflurane in 02 for 60 min as soon as reperfusion was started in group II and III . Wortmannin 0.6 mg/kg was administered iv at 30 rain before reperfusion in group III and/ IN. Neurological function was assessed and scored at 24, 48 and 72 h （T1-3 ） of reperfusion. The animals were decapitated after the last neurological function assessment. Their brains were immediately removed for determination of infarct size. The expression of phosphorylated Akt and Bad （p-Akt, p-Bad） were determined by Western-blot analysis in isehemic penumbra. Results Sevoflurane postconditioning significantly improved the neurological function, decreased the infarct size and increased the expression of p-Akt and p-Bad in group II as compared with group I . There was no significant difference in all variables between group I and group IV . Wortmannin attenuated the protective effect of sevoflurane postcoditioning against focal cerebral I/R injury. Conclusion Up-regulation of p-Bad expression induced by activation of PI3K/Akt signal pathway is involved in the protective effect of sevoflurane postconditioning against focal cerebral I/R injury. Key words: Anesthetics, inhalation ;  Brain ischemia ;  Reperfusion injury ;  Postconditioning