Effects of propofol on activation of c-Jun N-terminal kinase in hippocampus following asphyxial cardiac arrest-resuscitation in rats

Objective To investigate the effect of propofol on the activation of c-Jun N-terminal kinase (JNK) in hippocampus following asphyxial cardiac arrest-resuscitation in rats.Methods Forty male Sprague-Dawley rats,aged 6 months,weighing 350-380 g,were randomly divided into 4 groups (n =l0 each):sham operation group (group S),asphyxial cardiac arrest-cardiopulmonary resuscitation group (group CA-CPR),propofol group (group P) and normal saline group (group NS).All the rats were tracheostomized and mechanically ventilated after anesthetization.Cardiac arrest was induced by clamping the tracheal tube at the end of exhalation until ECG activity disappeared and MAP ＜ 10 mm Hg.Resuscitation was started 3 min later.MAP ＞ 60 mm Hg and HR ＞ 250 bpm were considered to be signs of successful resuscitation.Propofol 2 mg/kg was injected intravenously at 30 min before asphyxia,followed by propofol infusion at a rate of 4 mg· kg-1 · h-1 until the start of resuscitation in group P,while the equal volume of normal saline was given in group NS.At 12 h after successful resuscitation,the animals were sacrificed and brains were harvested for determination of wet/dry brain weight (W/D) ratio in brain tissues and expression of phosphor-JNK (p-JNK) in hippocampus (by immuno-histochemistry and Western blot),and for examination of the pathological changes of hippocampus.Results Compared with group S,W/D ratio was significantly increased and the expression of p-JNK in hippocampus was up-regulated in CA-CPR,P and NS groups (P ＜ 0.05 or 0.01).Compared with group CA-CPR,W/D ratio was significantly decreased and the expression of p-JNK in hippocampus was down-regnlated in group P (P ＜ 0.05 or 0.01),and no significant change was found in the indexes mentioned above in group NS (P ＞ 0.05).The pathological changes of hippocampus were significantly attenuated in group P compared with group CA-CPR.Conclusion Propofol can inhibit the activation of JNK in hippocampus following asphyxial cardiac arrest-resuscitation in rats and thus reducing brain injury. Key words: Propofol;  JNK mitogen-activated protein kinases;  Heart arrest;  Cardiopulmonary resuscitation ;  Reperfusion injury ;  Brain