摘要目的 评价机械通气诱发小鼠海马神经元凋亡与哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的关系.方法 健康雄性C57BL∕6小鼠50只,8～10周龄,体重20～25 g,采用随机数字表法分为2组(n=25):对照组(C组)和机械通气组(V组).C组自主呼吸,V组机械通气6 h.机械通气结束后1和3 d时行旷场实验和场景恐惧实验.机械通气结束后1 d时取海马组织,采用West-ern blot法检测mTOR、磷酸化mTOR(p-mTOR)、微管相关蛋白1轻链3Ⅱ(LC3Ⅱ)的表达,计算p-mTOR∕mTOR比值;采用TUNEL法检测海马神经元凋亡指数.结果 与C组比较,V组中央区停留时间延长,跨格次数减少,僵直时间百分比降低,LC3Ⅱ表达上调,p-mTOR∕mTOR比值和凋亡指数升高(P<0.05).结论 机械通气诱发小鼠海马神经元凋亡的机制可能与mTOR信号通路激活有关.

abstractsObjective To evaluate the relationship between mechanical ventilation-induced apoptosis in hippocampal neurons and mammalian taget of rapamycin ( mTOR) signaling pathway in mice. Methods Fifty healthy male C57BL∕6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 2 groups ( n=25 each) using a random number table method: control group ( group C ) and mechanical ventilation group ( group V) . The mice breathed spontaneously for 6 h in group C, and the mice were mechanically ventilated for 6 h in group V. Open field test and contextual fear conditioning test were conducted at 1 and 3 days after the end of ventilation. Hippocampal tissues were obtained at 1 day after the end of ventilation for determina-tion of the expression of mTOR, phosphorylated mTOR (p-mTOR), microtubule-associated protein 1 light chain 3Ⅱ( by Western blot) and apoptosis in hippocampal neurons ( by TUNEL) . The p-mTOR∕mTOR ratio and apoptosis index were calculated. Results Compared with group C, the time animals spent in the central square was significantly prolonged, the number of crossing the grid was reduced, the percentage of freezing time was decreased, the expression of microtubule-associated protein 1 light chain 3Ⅱwas up-regulated, and the p-mTOR∕mTOR ratio and apoptosis index were increased in group V ( P<0. 05) . Conclusion The mech-anism by which mechanical ventilation induces apoptosis in hippocampal neurons may be related to activation of mTOR signaling pathway in mice.