Effect of dexmedetomidine on activity of GSK-3β during propofol-induced apoptosis in hippocampal nerve cells of newborn rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of dexmedetomidine on the activity of glycogen synthase kinase-3 beta (GSK-3β) during propofol-induced apoptosis in hippocampal nerve cells of newborn rats.Methods Sixty male 7-day-old Sprague-Dawley rats,weighing 10-15 g,were divided into 6 groups (n=10 each) using a random number tablenormal saline group (group NS),fat emulsion group (group F),propofol group (group P) and different doses of dexmedetomindine groups (group D25,group D50 and group D75).Normal saline and fat emulsion 100 μl were injected intraperitoneally in group NS and group F,respectively.In group P,propofol 50 mg/kg was intraperitoneally injected,and an increment of propofol 50 mg/kg was added after righting reflex completely recovered,with the total amount of 100 mg/kg.In group D25,group D50 and group D75,dexmedetomidine 25,50 and 75 μg/kg were intraperitoneally injected,respectively,and 30 min later propofol 100 mg/kg was administered.At 2 h after emergence,the rats were sacrificed,their brains were removed for determination of apoptosis in hippocampal nerve cells (by TUNEL),and the hippocampi were isolated for detection of the expression of GSK-3β and phosphorylated GSK-3β (p-GSK-3β) by Western blot analysis.The apoptosis index (AI) and ratio of p-GSK-3β/GSK-3β were calculated.Results Compared with group NS,AI was significantly increased,the expression of p-GSK-3β was down-regulated,and the p-GSK-3β/GSK-3β ratio was decreased in P,D25,D50 and D75 groups (P＜0.05).Compared with group P,AI was significantly decreased,the expression of p-GSK-3β was up-regulated,and the p-GSK-3β/GSK-3β ratio was increased in D25,D50 and D75 groups (P＜0.05).Compared with group D25,AI was significantly decreased (P＜0.05),and no significant change was found in the expression of p-GSK-3β or ratio of p-GSK-3β/GSK-3β in D50 and D75 groups (P＞0.05).Compared with group D50,AI was significantly decreased (P＜0.05),and no significant change was found in the expression of p-GSK-3β or ratio of p-GSK-3β/GSK-3β in group D75 (P＞0.05).Conclusion The mechanism by which dexmedetomidine attenuates propofol-induced apoptosis in hippocampal nerve cells may be related to inhibition of GSK-3β activity in newborn rats.