右美托咪定对严重烫伤大鼠心肌细胞凋亡时PI3K/Akt/GSK-3β通路的影响  

Effect of dexmedetomidine on PI3K/Akt/GSK-3β signaling pathway during apoptosis in cardiomyocytes of rats with severe scald

作　　者：王惠枢[1] 张思多[1] 范崇玖[1] 徐晓东[1] 林蕾[1] 张良成[1] Wang Huishu;Zhang Siduo;Fang Chongjiu;Xu Xiaodong;Lin Lei;Zhang Liangcheng(Department of Anesthesiology, Affiliated Union Hospital of Fujian Medical University, Fuzhou 350001, China)

机构地区：[1]福建医科大学附属协和医院麻醉科,福州市350001

出　　处：《中华麻醉学杂志》2018年第10期1258-1260,共3页Chinese Journal of Anesthesiology

基　　金：福建省科技厅自然科学基金项目(2015J05155).

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220~280g,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30μg/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12h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。Objective 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 Sprague-Dawley 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.

关 键 词：右美托咪啶 MAP激酶信号系统 细胞凋亡 心肌 烧伤 

分 类 号：R614[医药卫生—麻醉学]