JNK信号通路在大鼠窒息性心跳骤停复苏后脑损伤中的作用  

Role of JNK signal pathway in brain injury after resuscitation in a rat model of asphyxia cardiac arrest

作　　者：陈龙 左明章[3] 刘功俭[2] 陈西艳 张岩 成勤[2] 张茂银[2] 

机构地区：[1]徐州市第六人民医院麻醉科,221006 [2]徐州医学院附属医院麻醉科江苏省麻醉学重点实验室 [3]卫生部北京医院麻醉科

出　　处：《中华麻醉学杂志》2012年第1期93-95,共3页Chinese Journal of Anesthesiology

基　　金：江苏省“六大人才高峰”基金项目（06-B-065）;徐州市铜山区社会发展基金项目（TS005）

摘　　要：目的评价c-Jun氨基端激酶（JNK）信号通路在大鼠窒息性心跳骤停复苏后脑损伤中的作用。方法健康雄性SD大鼠40只，体重300～350g，采用随机数字表法，将其随机分为4组（Ⅱ=10）：假手术组（SH组）、心跳骤停组（CA组）、JNK抑制剂SP600125组（SP组）和二甲基亚砜组（DMSO组）。静脉注射维库溴铵2mg／kg后行机械通气，维持PErcO235—45mmHg。CA组、SP组和DMSO组机械通气稳定5min后注射维库溴铵1mg／kg，1min后停止机械通气，于呼气末时夹闭气管导管，制备窒息性心跳骤停模型。心跳骤停3min后，开放气管导管行机械通气，立即进行复苏。SP组静脉注射SP60012520mg／kg，DMSO组静脉注射DMSO0．2ml。于心跳恢复后5h时处死大鼠，取脑组织，测定湿，干重比（W／D比）和细胞凋亡情况，观察病理学结果。结果与SH组比较，CA组、SP组和DMSO组脑组织W／D比和凋亡细胞计数升高（P〈0．05）；与CA组和DMSO组比较，SP组脑组织W／D比和凋亡细胞计数下降（P〈0．05），病理学损伤减轻；CA组和DMSO组脑组织W／D比和凋亡细胞计数比较差异无统计学意义（P〉0．05）。结论JNK信号通路参与了大鼠窒息性心跳骤停复苏诱发脑损伤的病理生理过程。Objective To evaluate the role of JNK signal pathway in brain injury after resuscitation in a rat model of asphyxia cardiac arrest. Methods Forty healthy male SD rats weighing 300-350 g were randomly divided into 4 groups （n = 10 each）： sham operation group （group SH）; cardiac arrest group （group CA）; group SP600125-JNK inhibitor （group SP） and dimethyl sulfexide （DMSO） group. The rats were anesthetized with intraperitoneal pentobarbital 45 mg/kg, tracheostomized and mechanically ventilated. PET CO2 was maintained at 35-45 mm Hg. Femoral artery and vein were cannulated for BP monitoring and fluid infusion. Cardiac angst was induced by clamping tracheal tube until ECG activity disappeared and MAP 〈 10 mm Hg. Resuscitation was started at 3 min after cardiac arrest. MAP 〉 60 mm Hg and HR 〉 250 bpm were considered to be signs of successful resusci- tation. SP600125 20 mg/kg and DMSO 0.2 ml were injected iv as soon as chest compression was started in groups SP and DMSO respectively. The animals were sacrificed at 5 h after successful resuscitation and their brains were removed for determination of wet/dry （W/D） weight ratio and microscopic examination of hippocampus. Neuronal apoptosis was detected by TUNEL. Results Cardiac arrest significantly increased W/D ratio and the number of apoptotic cells in group CA. SP600125 iv significantly attenuated the cardiac arrest-induced increase in W/D ratioand the number of apoptotic cells but DMSO did not. Conclusion JNK signal pathway is involved in the brain injury after resuscitation in a rat model of asphyxia cardiac arrest.

关 键 词：JNK丝裂原活化蛋白激酶类 窒息 心脏停搏 脑损伤 

分 类 号：R614[医药卫生—麻醉学]