δ阿片受体激动剂在全脑缺血再灌注损伤中的神经保护机制  

The neuroprotective machanism of Delta-opioid receptor activator against global cerebral ischemia-reperfusion

作　　者：韩洁韵[1] 梁庆[1] 彭翔[1] 黄伟青[1] 梁子敬[1] 

机构地区：[1]广州医科大学附属第一医院急诊科,广州510120

出　　处：《中国神经精神疾病杂志》2017年第8期449-452,共4页Chinese Journal of Nervous and Mental Diseases

基　　金：广州市医药卫生科技项目(编号:20141A011078)

摘　　要：目的观察δ阿片受体激动剂DADLE对大鼠全脑缺血再灌注后神经元凋亡细胞及磷酸化p38表达的影响,探讨DADLE在全脑缺血再灌注损伤细胞凋亡中的脑保护机制。方法采用二血管加低血压阻断法建立大鼠全脑缺血再灌注模型,随机分为假手术组(n=10),模型组(n=10),治疗组(再按DADLE静脉注射不同剂量分为3个亚组2 mg组、3 mg组、5 mg组,n=10),TUNEL法检测凋亡细胞,Western blot检测神经元磷酸化p38丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)蛋白的表达。结果 DADLE可显著减少大鼠缺血神经元细胞凋亡,与假手术组比较,缺血后大鼠神经元磷酸化p38 MAPK表达水平增加(P<0.05),与模型组比较,治疗组各组磷酸化p38 MAPK表达水平有所降低(LSD-t值依次为0.61、1.61、1.8,P<0.05),且其作用呈剂量依赖性。结论δ阿片受体激动剂DADLE对大鼠全脑缺血再灌注损伤有神经保护作用,抑制磷酸化p38 MAPK的表达,减少细胞凋亡是其脑保护作用机制之一。Objective To investigate the effects of Delta-opioid receptor activator DADLE on the expression of the p38 MAPK and the neuronal apoptosis after global cerebral ischemia-reperfusion and explore the neuroprotective mechanisms of DADLE. Methods Global cerebral ischmemia-reperfusion models in rats were induced by bilateral common carotid artery occlusion combined with hypotension. Rats were randomly divided into sham group（ n=10）, ischemia-reperfusion group（n=10） and three treatment groups with different doses of DADLE（2 mg group, 3 mg group,5 mg group, n=10）. TUNEL method and Western blot analysis were used to measure apoptotic neurons and expression levels of p38 MAPK phosphorylation, repectively. Results DADLE treatment significantly reduced neuron apoptosis（P〈0.05）. The expression levels of p38 MAPK were increased in ischemia-reperfusion group than in sham group（ P〈0.05）. In DADLE treated groups, the expression levels of p38 MAPK were dose-dependently decreased compared with the ischemia-reperfusion group. Conclusion Delta-opioid receptor activator DADLE can be neuroprotective against global I/R injury. Attenuation of apoptosis and p38 MAPK signal pathway might be involved in the neuroprotective mechanism of DADLE.

关 键 词：受体 阿片样 δ 再灌注损伤 细胞凋亡 

分 类 号：R743[医药卫生—神经病学与精神病学]