摘要
目的：探讨WIN55，212-2药物性低温在心肺复苏后对神经细胞凋亡的作用。方法健康SD大鼠经食道直流电刺激建立心脏骤停模型。成功诱导后5 min行心肺复苏，恢复自主循环的大鼠存活30 min后，随机（随机数字法）分为3组（n＝10／组）： WIN55，212-2组（W组， WIN55，212-2，1 mg／（kg· h）、常温对照组：等体积的5％DMSO＋37℃（NT组）、 WIN55，212-2＋37℃组（W＋NT组， WIN55，212-2，1 mg／（kg· h）；用药时间维持4 h后， WIN55，212-2组复温2 h达37℃，观察ROSC后3组大鼠72h内的存活情况及神经功能评分。相同方法再次建立上述3组动物模型，分别于24 h、48 h、72 h在各组中随机选取5只大鼠，通过 HE 染色法观察脑组织形态学变化以及通过TUMEL法观察脑组织海马CA1区神经元细胞凋亡情况。结果 W组大鼠的体温在4 h内逐渐由37℃降到34℃。 W组大鼠的累积生存率明显高于W＋NT组及NT组（ P＝0.02）。 W组大鼠的神经功能评分较W＋NT组和NT组明显改善（ P＜0.05）。 W组大鼠神经细胞病理损伤以及神经细胞凋亡情况较其余两组少。 W＋NT组大鼠的病理损伤及凋亡情况介于两者之间。结论 WIN55，212-2在心肺复苏后诱导大鼠低温，延长存活时间，改善神经系统功能。其作用可能与WIN55，212-2减轻脑组织病理损伤、减少神经细胞凋亡有关。
Objective To investigate the pharmacological hypothermic effect of WIN55, 212-2 on neuronal apoptosis after cardiopulmonary resuscitation. Methods Cardiac Arrest （ CA ） was induced in Sprague-Dawley rats.Five minutes after onset of CA, cardiopulmonary resuscitation （ CPR） was carried out.At 30 minutes post-resuscitation, the animals were randomized into three groups （n=10 in each group）： （1） WIN55, 212-2 hypothermia group [W group, WIN55, 212-2, 1 mg/（kg·h）].（2） Normothermia group （NT group, 5%DMSO）;（3） WIN55, 212-2 with normothermia group （W＋NT group, WIN55, 212-2, 1 mg/（kg·h）.Animals in WIN55, 212-2 hypothermia group and WIN55, 212-2 with normothermia group were dealt with continuous intravenous infusion of WIN55, 212-2 [1 mg/（kg·h）] for 4 h, while rats in NT group were infused with equal volume of 5% DMSO instead.The survival time and neurological deficit score （ NDS） were observed.The CA models were established in three groups.After rats were sacrificed, the brains were harvested for detecting histopathological changes and apoptosis of neural cell at 24 h, 48 h and 72 h after ROSC respectively.Five animals of each group were chosen randomly （ random number ） .Results Body temperatures of rats in W group decreased from 37℃ to 34℃ in 4 hours.Accumulated survival rate in W group was higher than that in the other two groups （ P=0.02） .NDS was significantly improved in W group than that in the other two groups （ P〈0.05） .Morphological change in W group was less serious than that in the other two groups.The number of neuron apoptosis in W group was smaller than that in the other two groups.Conclusions WIN55, 212-2 inducing pharmacologically hypothermia during post-resuscitation prolonged survival and improved cerebral function in rat cardiac arrest models.The beneficial effects of WIN55, 212-2 were associated with ameliorating the histopathological damage in brain and alleviating the neuron apoptosis.
出处
《中华急诊医学杂志》
CAS
CSCD
北大核心
2016年第4期455-459,共5页
Chinese Journal of Emergency Medicine
基金
国家自然科学基金（81460289,81201447）
广西自然科学基金（2012GXNSFBA053086,2013GXNSFAA019189）
关键词
心肺复苏
WIN55
212-2
药物性低温
凋亡
Cardiopulmonary resuscitation
WIN55, 212-2
Pharmacological hypothermia
Apoptosis
