β-内啡肽在中枢吗啡预处理减轻大鼠心肌缺血后损伤中的作用  

The role of beta-endorphin in protective effect of intracerebroventricular morphine preconditioning against myocardial post-ischemic injury in rats

作　　者：程新琦[1] 张野[1,2] 陆姚[2] 李锐[1] 翁立军[2] 陈志武[3] 

机构地区：[1]安徽医科大学附属第一医院麻醉科,安徽合肥230022 [2]安徽医科大学附属第二医院麻醉科,安徽合肥230601 [3]安徽医科大学药理学教研室,安徽合肥230032

出　　处：《中国药理学通报》2009年第9期1152-1156,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助课题(No30672032);安徽省优秀青年基金资助项目(No08040106814)

摘　　要：目的观察中枢与外周β-内啡肽对缺血后心肌的影响及其在侧脑室吗啡预处理减轻大鼠心肌缺血/再灌注损伤中的含量变化,探讨β-内啡肽在中枢吗啡预处理在体大鼠缺血后心肌保护作用中的角色。方法66只♂SD大鼠,分别建立侧脑室微量注射和心肌缺血/再灌注损伤动物模型。随机分为假手术(Sham)组、缺血对照(CON)组、缺血预处理(IPC)组、中枢和外周β-内啡肽激动剂(Icv/Iv-EP)组、中枢吗啡预处理(MPC组)、中枢β-内啡肽阻断剂(Icv-MPC-Anti-EP/Icv-Anti-EP-MPC)组、外周β-内啡肽阻断剂(Icv-MPC+Iv-Anti-EP)组、中枢和外周β-内啡肽阻断剂自身对照(Icv/Iv-Anti-EP)组。观察平均动脉压(MAP)、心率(HR)、压力心率乘积(RPP)、缺血危险区(AAR)、梗死区(IS)体积、IS/AAR等的变化;同时以免疫组化观察下丘脑弓状核(arcuate nucleus,ARC),中脑导水管周围灰质(periaque-ductalgray,PAG)及左室心肌(myocardium of left ventricle,MC)β-内啡肽的阳性表达。结果与CON组相比,IPC、MPC、Icv-EP、Iv-EP、Icv-Anti-EP-MPC、Icv-MPC+Iv-Anti-EP组均明显降低IS/AAR(P<0.01);Icv-MPC-Anti-EP组虽然取消MPC的保护效应(P<0.01),但较CON组差异仍有统计学意义(P<0.05);与CON组相比,MPC组减弱了ARC中β-内啡肽的阳性表达(P<0.05),同时明显增强PAG和左室心肌的免疫反应强度(P<0.05;P<0.01)。结论中枢与外周β-内啡肽对缺血后心肌损伤有保护作用;侧脑室吗啡预处理后可能促进下丘脑弓状核释放β-内啡肽,后者作为神经递质部分参与了中枢吗啡预处理介导的心肌保护效应。Aim To investigate the effect of central and peripheral beta-endorphin after myocardial ischemiareperfusion injury in rats and their concentration changes and the role on cardioprotection after intracerebroventricular morphine preconditioning. Methods Sixtysix Sprague-Dawley rats were established intracerebroventricular catheter placement and myocardial ischemia/ reperfusion models and randomly assigned to 11 groups： Ⅰ sham group; Ⅱischemic control （CON） group ; Ⅲischemic preconditioning （ IPC ） group ; Ⅳcentral administration of beta-endorphin （Icv-EP） group; Ⅴperipheral injections of beta-endorphin （Iv- EP） group; Ⅵcentral morphine preconditioning （MPC） group ; Ⅶ- Ⅷcentral administration of antibeta-endorphin （ Icv-MPC-Anti-EP/Icv-Anti-EP-MPC ） group; Ⅸperipheral injections of anti-beta-endorphin （ Icv-MPC ＋ Iv -Anti-EP） group and Ⅹ-Ⅺself control of anti-beta-endorphin （ Icv/Iv-Anti-EP ） group. MAP,HR and RPP（SP ×HR） were recorded;the volume of area at risk （ AAR）, infarct size （ IS ） and the area of myocardial infarction, which was demonstrated by IS/AAR were calculated; meanwhile, the intensity of beta-endorphin immuoreactivity was tested by immunohistochemic technique in hypothalamic arcuate nucleus （ ARC）, periaqueductal gray （PAG） and myocardium of left ventricle （MC）. Results IS/AAR was reduced significantly by IPC, MPC, Icv-EP, Iv-EP, Icv-Anti-EPMPC and Icv-MPC ＋ Iv-Anti-EP（ P 〈 0. 01 ）, compared to CON; Icy- MPC-Anti-EP abolished protective effect of MPC（P 〈0.01 ）, but there was also difference compared with control group （ P 〈 0. 05 ）. The intensity of beta-endorphin immuoreactivity in MPC was decreased in ARC （ P 〈 0. 05 ） and intensified significantly in PAG and MC（P 〈 0.01 ）versus CON. Conclusions Central and peripheral beta-endorphin produces protective effects after myocardial ischemic injury;protection elicited by central morphine preconditioning against myocardial ischemia-reperfus

关 键 词：Β-内啡肽 侧脑室 缺血/再灌注损伤 弓状核 中脑导水管周围灰质 神经递质 

分 类 号：R-332[医药卫生] R322.11