CREB磷酸化蛋白水平对δ阿片受体激动剂后处理脑保护作用的影响  

Involvement of CREB phosphorylation in the neuroprotection induced by δ opioid receptor agonist postconditioning in the asphyxial cardiac arrest rat model

作　　者：杨璐[1] 赵晓勇[1] 孙美艳[1] 高昌俊[1] 柴伟[1] 

机构地区：[1]第四军医大学唐都医院麻醉科,西安市710038

出　　处：《临床麻醉学杂志》2013年第5期484-487,共4页Journal of Clinical Anesthesiology

基　　金：国家自然科学基金(81071527)

摘　　要：目的建立大鼠窒息性心肺复苏脑损伤模型,探讨环磷酸腺苷反应元件结合蛋白(CREB)磷酸化蛋白在δ阿片受体(DOR)激动剂BW373U86后处理对心肺复苏脑损伤的保护作用。方法健康成年雄性SD大鼠随机分为四组:假手术组(Sham组)、模型组(ACA组)、激动剂组(BW组)和拮抗剂组(Nal组)。除Sham组外,均采用8min窒息法建立大鼠窒息性心肺复苏脑损伤模型。自主循环恢复(ROSC)后,ACA组和BW组分别静脉给予生理盐水1ml和BW373U861mg/kg;Nal组在静脉给予BW373U861mg/kg前,静注DOR拮抗剂Naltrindole1mg/kg。观察四组大鼠复苏成功率,ROSC后1、2、3、7d对存活大鼠进行神经功能缺损评分,观察复苏后大鼠CREB磷酸化水平和mRNA表达的变化,以及海马CA1区神经元的损伤情况。结果与Sham组比较,ACA组、BW组和Nal组海马组织中磷酸化的CREB(pCREB)蛋白相对表达明显升高(P<0.05),ROSC后各时点神经功能缺损评分均降低(P<0.05);海马CA1区存活神经元数明显减少(P<0.05)。与ACA组比较,BW组海马组织中pCREB蛋白相对表达升高、ROSC后各时点神经功能缺损评分升高(P<0.05)。与BW组比较,Nal组海马组织中pCREB蛋白相对表达降低,ROSC后各时点神经功能缺损评分降低(P<0.05),海马CA1区中ACA组和Nal组存活神经元数减少,病理损伤加重(P<0.05)。结论 CREB的磷酸化可能参与了DOR激动剂BW373U86后处理对心肺复苏脑损伤的保护作用。Objective To investigate the involvement of cAMP response element binding protein （CREB） phosphorylation in the neuroprotection induced by δ opioid receptor（DOR） agonist postconditioning in the asphyxial cardiac arrest rat model. Metlmds Adult male SD rats were randomly divided into four groups： group Sham, Asphyxial cardiac arrest group （group ACA）, DOR agonist group （group BW）, and IOR antagonist group（group Nal）. Except for group Sham, cardiac arrest was induced in the other three groups by clamping the tracheal tubes for eight minutes in rats and the animals were resuscitated by a standard method. DOR agonist BW373U86 1 mg/kg was administrated immediately after restoration o{ spontaneous circulation （ROSC）. The survival rate after resuscitation was record. Expressions of CREB phosphorylation and mRNA were detected 24 h after ROSC. The neurological deficit score（NDS） was evaluated at 1 d, 2 d, 3 d, and 7 d after ROSC. And then the rats were sacrificed for nissl staining. These effects were then evaluated in the presence of DOR antagonist Naltrindole 1 mg/kg, which was ad ministrated before BW373U86 injeetiorL Results The phosphorylation of CREB in the other three groups was increased as compared with Sham group （P〈0. 05）, whereas neurological outcome and the number of vial neurons in hippocampus were reduced as compared with group Sham （P〈0.05）. Compared with group ACA, BW group had up-regulated phosphorylated CREB, improved neurological outcome, and increased number of vial neurons in hippocampus （P〈0. 05）. These neuroproteetive effeets were antagonized by IX）R antagonist Naltrindole. ColldllSiOn CREB phosphorylation could be involved in the neuroprotective effects induced by DOR agonist BW373U86 postconditioning in the asphyxia cardiac arrest rat model.

关 键 词：Δ阿片受体 再灌注损伤 环磷酸腺苷反应元件结合蛋白 脑保护 

分 类 号：R965[医药卫生—药理学]