Effect of sevoflurane preconditioning on mitocbondrial permeability transition pore following focal cerebral ischemia-reperfusion injury in rats

Abstract

Objective To investigate the effect of sevoflurane preconditioning on mitochondrial permeability transition pore (mPTP) following focal cerebral ischemia-reperfusion (I/R) injury. Methods Male adult SD rats weighing 250-280 g were randomly assigned into 5 groups ( n = 12 each): group Ⅰ sham operation(group S); group Ⅱ focal cerebral ischemia-reperfusion (group I/R); group Ⅲ sevoflurane preconditioning + I/R(group Sev); group Ⅳ 5-HD + Sev + I/R and group Ⅴ 5-HD + I/R. Focal cerebral I/R was induced by right middle cerebral artery occlusion (MCAO). A 50 mm long 4.0 nylon thread was inserted into right internal carotid artery and advanced cephalad until resistance was met. MCAO was maintained for 2 h followed by 24 h reperfusion in group Ⅱ-Ⅴ. In group Ⅲ the animals inhaled 2.4% sevoflurane for 60 min at 24 h before I/R. In group Ⅳ 5-HD 40 mg/kg was injected intraperitoneally at 30 min before sevoflurane preconditioning. In group Ⅴ 5-HD 40 mg/kg was injected IP at 30 min before MCAO. The animals were decapitated at 24 h of reperfusion. The parietal cortex of the ischemic side was isolated. Spectrophotometry was used to measure the mPTP activity. The expression of Bcl-2 and Bax protein (by Western blotting) and neuronal apoptosis (by TUNEL) were determined.Results Sevoflurane preconditioning significantly inhibited the activity of mPTP, reduced neuronal apoptosis induced by I/R and increased Bcl-2 protein expression but had no significant effect on Bax protein expression. The protective effects of sevoflurane preconditioning against cerebral I/R were blocked by 5-HD. Conclusion Sevoflurane could inhibit the mitochondrial permeability transition and reduce neuronal apoptosis via activation of mito-KATP channel and up-regulation of Bcl-2 expression. Key words: Mitochondrial membrane transport proteins; Anesthetics, inhalation; Reperfusion injury; Brain; Apoptosis