氯化锂预先给药对老龄大鼠腹部手术后认知功能的影响

目的 探讨氯化锂预先给药对老龄大鼠腹部手术后认知功能的影响.方法 雄性SD大鼠48只,18月龄,体重550～700 g,随机分为3组(n=16):对照组(C组)、手术组(O组)和氯化锂预处理组(L组).L组腹腔注射氯化锂2 mmol/kg,1次/d,连续7 d,C组和O组给予等容量生理盐水.给药结束后O组和L组行腹部手术,术后24 h时测定海马IL-1β含量、总糖原合成酶激酶3β(GSK-3β)和磷酸化GSK-3β(p-GSK-3β)的表达水平,术后4～6 d行Morris水迷宫实验(记录逃逸潜伏期和游泳距离).结果 与C组比较,O组术后4～6 d逃逸潜伏期和游泳距离延长,海马IL-1β含量升高,p-GSK-3β表达下调,L组术后4 d游泳距离延长,海马IL-1β含量降低(P＜0.05),O组和L组总GSK-3β表达差异无统计学意义(P＞0.05);与O组比较,L组逃逸潜伏期和游泳距离缩短,海马IL-1β含量降低,p-GSK-3β表达上调(P＜0.05),总GSK-3β表达差异无统计学意义(P＞0.05).结论 氯化锂预先给药可改善老龄大鼠术后认知功能,其机制与抑制海马GSK-3β的活性,减轻海马炎性反应有关.

Effects of lithium chloride pretreatment on cognitive function after laparotomy in aged rats

Objective To investigate the effects of lithium chloride pretreatnent on cognitive function after laparotomy in aged rats. Methods Forty-eight male SD rats aged 18 months, weighing 550-700 g were randomly divided into 3 groups (n = 16 each): group Ⅰ control (group C); group Ⅱ operation (group O) and group Ⅲ lithium chloride preconditioning (group L). In group L lithium chloride 2 mmol/kg was injected intraperitoneally (IP) once a day for 7 consecutive days before exploratory laparotomy. In group C and group O equal volume of normal saline was injected instead of lithium chloride. The animals were anesthetized with IP 2 % pentobarbital 0.25 ml/100 g. Morris water-maze (MWM) test was performed at day 4-6 after operation in 8 animals in each group. Another 8 animals were killed at 24 h after operation and their brains were immediately removed for determination of IL-1β content and expression of total glycogen synthase kinase-3β (GSK-3β) and p-GSK-3β in hippocampus by ELISA and Western blot respectively. Results Compared with group C the escape latency and swimming distance were both significantly prolonged at day 4-6 after operation in group O, while in group L only swimming distance was prolonged at day 4 after operation. The IL-1β content in hippocampus was significantly higher and the expression of p-GSK-3β was significantly lower in group O than in group C and L. There was no significant difference in total GSK-3β among the 3 groups. Conclusion Lithium chloride pretreatment can improve the cognitive function after laparotomy in aged rats by inhibiting GSK-3β activity and attenuating inflammatory response in hippocampus.