摘要目的 评价右美托咪定对严重烫伤大鼠心肌细胞凋亡时磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/糖原合成酶激酶3β(GSK-3β)通路的影响.方法 健康成年雄性SD大鼠24只,体重220～280 g,采用随机数字表法分为3组(n=8):对照组(C组)、烫伤组(S组)和右美托咪定组(D组).将大鼠背部浸入94℃热水中12s,制备大鼠30％体表面积Ⅲ度烧伤模型.C组大鼠背部浸入37 ℃温水中12s,D组大鼠烫伤后即刻腹腔注射2μg/ml右美托咪定30 μg/kg.大鼠烫伤后按Parkland公式腹腔注射等渗盐水抗休克治疗,C组不注射.处理后12 h麻醉下迅速剖开胸腔,取左室心肌组织,-80℃保存.采用TUNEL法检测心肌细胞凋亡情况,计算细胞凋亡指数(AI),Westernblot法检测PI3K、磷酸化Akt (p-Akt)和磷酸化GSK-3β(p-GSK-3β)的表达.结果 与C组比较,S组和D组大鼠AI升高,心肌PI3K、p-Akt和p-GSK-3β表达上调(P＜0.05);与S组比较,D组大鼠AI降低,心肌PI3K、p-Akt和p-GSK-3β表达上调(P＜0.05).结论 右美托咪定可通过进一步激活PI3K/Akt/GSK-3β通路抑制严重烫伤大鼠心肌细胞凋亡.

abstractsObjective To evaluate the effect of dexmedetomidine on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3 beta (GSK-3β) signaling pathway during apoptosis in cardiomyocytes of rats with severe scald.Methods Twenty-four healthy adult male SpragueDawley rats,weighing 220-280 g,were divided into 3 groups (n=8 each) using a random number table method:control group (group C),severe scald group (group S) and dexmedetomidine group (group D).Thirty percent of the total body surface area was shaved on the back and then exposed to 94 ℃ water (with 37 ℃ warm water in group C) for 12 s to establish the model of third degree scald in pentobarbital sodium-anesthetized rats.Dexmedetomidine 30 μg/kg (2 μg/ml) was intraperitoneally injected immediately after scald in group D.Rats received anti-shock treatment by intraperitoneal injection of isotonic saline according to Parkland formula,and group C received no injection.Rats were anesthetized using the method previously mentioned at 12 h after treatment,and myocardial specimens of the left ventricle were rapidly excised and stored at-80 ℃ for determination of cell apoptosis (by TUNEL) and expression of P13K,phosphorylated Akt (p-Akt) and phosphorylated GSK-3β (p-GSK-3β) (by Western blot).Apoptosis index (AI) was calculated.Results Compared with group C,AI was significantly increased,and the expression of P13K,p-Akt and p-GSK-3β was up-regulated in S and D groups (P＜0.05).Compared with group S,AI was significantly decreased,and the expression of P13K,p-Akt and p-GSK-3β was up-regulated in group D (P＜0.05).Conclusion Dexmedetomidine inhibits apoptosis in cardiomyocytes through activating PI3K/Akt/GSK-3β signaling pathway in the rats with severe scald.