右美托咪定对异丙酚诱导新生大鼠海马神经细胞凋亡时GSK-3β活性的影响

Effect of dexmedetomidine on activity of GSK-3β during propofol-induced apoptosis in hippocampal nerve ceils of newborn rats

目的评价☆美托咪定对异丙酚诱导新生大鼠海马神经细胞凋亡时糖原合成酶激酶-3β（GSK-3β）活性的影响。方法雄性SD大鼠60只，7日龄，体重10～15g，采用随机数字表法分为6组（n=10）：生理盐水组（Ns组）、脂肪乳剂组（F组）、异丙酚组（P组）和不同齐Ij量右美托咪定组（D25组、D50组和D75组）。Ns组及F组分别腹腔注射生理盐水、脂肪乳剂100μl；P组先腹腔注射异丙酚50mg／kg，待翻正反射恢复后，再追加50mg／kg，总量为100mg／kg；D25组、D50组和D75组分别九腹腔注射右美托咪定25、50和75μg／kg，30min后再给予异丙酚。分别于大鼠苏醒后2h，取脑组织，采用TUNEL法确定海马神经细胞凋亡指数（AI）；分离海马组织，采用Westernblot法测定海马GSK-3β及磷酸化GSK-3β（p-GSK-3β）的表达水平，计算p-GSK-3β／GSK-3β比值。结果与NS组比较，P组、D25组、D50组和D75组海马神经细胞AI升高，p-GSK-3β表达下调，p-GSK-35／GSK-3β比值降低（P〈0．05）；与P组比较，D25组、D50组和D75组海马神经细胞AI降低，p—GsK-3β表达上调，p-GSK-35／GSK-3β比值升高（P〈0．05）；与D25组比较，D50组和D75组海马神经细胞AI降低（P〈0．05），p-GSK-35表达及p-GSK-35／GSK-3β比值差异无统计学意义（_P〉0．05）；与D，。组比较，D50组海马神经细胞AI降低（P〈0．05），p-GSK-3β表达及p-GSK-35／GSK-3β比值差异无统计学意义（P〉0．05）。结论右美托咪定减轻异丙酚诱导新生大鼠海马神经细胞凋亡的部分机制可能与抑制GSK-3β活性有关。

Objective To evaluate the effect of dexmedetomidine on the activity of glycogen sy.- thase kinase-3 beta （GSK-3[3） during prupofol-indueed apoptosis in hippocampal nerve cells of newhorn 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 table： normal 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 in- jected, 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 eells （ by TUNEL） , and the hippoeampi were isolated for detection of the expression of GSK-3β and phosphoryl- ated 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 expres- sion of p-GSK-313 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, Ds0 and D75 groups （P〈 0.05）. Compared with group D25, Ar 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-indueed apoptosis in hippoeampal nerve cells may be related to inhibition of GSK-3β activity in newborn rats.