Role of mitochondriai permeability transition pore in reduction of brain injury by sevoflurane post-conditioning in a rat model of hemorrhagic shock and resuscitation / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of mitochondrial permeability transition pore (mPTP)in reduction of brain injury by sevoflurane postconditioning in a rat model of hemorrhagic shock and resuscitation (HSR).Methods Ninety pathogen-free healthy adult male Sprague-Dawley rats,weighing 300-350 g,were divided into 5 groups (n =18 each) using a random number tablesham operation group (group S),group HSR,sevoflurane postconditioning group (group SP),sevoflurane postconditioning plus atractyloside (ATR,a specific mPTP opener) group (group SP + ATR) and ATR group.Hemorrhagic shock was produced by withdrawing 40％ of the total blood volume from the right carotid artery over an interval of 30 min,and 1 h later the animals were resuscitated by infusion of the shed blood via the left jugular vein over 30 min.SP and SP+ATR groups were exposed to 2.4％ sevoflurane for 30 min starting from the onset of reinfusion.In ATR and SP+ATR groups,ATR 5 mg/kg was intravenously injected at 10 min before reinfusion.Six rats in each group were randomly sacrificed at 24 h after the end of autologous blood reinfusion,and the hippocampus was harvested for determination of the expression of Bcl-2 and Bax in hippocampal tissues (by Western blot) and degree of mPTP opening.At 72 h after the end of autologous blood reinfusion,the rest 6 rats in each group were selected and underwent Morris water maze test,and the cognitive function was evaluated.Results Compared with group S,the escape latency was significantly prolonged,the number of crossing the original platform and locomotor distance in the target quadrant were decreased,the expression of Bcl-2 was down-regulated,the expression of Bax was up-regulated,and the degree of mPTP opening was increased in group HSR (P＜0.05).Compared with group HSR,the escape latency was significantly shortened,the number of crossing the original platform and locomotor distance in the target quadrant were increased,the expression of Bcl-2 was up-regulated,the expression of Bax was down-regulated,and the degree of mPTP opening was decreased in group SP (P＜0.05),and no significant change was found in each parameter in ATR and SP+ATR groups (P＞0.05).Compared with group SP,the escape latency was significantly prolonged,the number of crossing the original platform and locomotor distance in the target quadrant were decreased,the expression of Bcl-2 was down-regulated,the expression of Bax was up-regulated,and the degree of mPTP opening was increased in group SP+ATR (P＜0.05).Conclusion The mechanism by which sevoflurane postconditioning ameliorates brain injury may be related to inhibiting mPTP opening in a rat model of HSR.