脊髓腺苷受体介导侧脑室吗啡预处理对大鼠缺血后心肌的保护作用  

Cardioprotective effect of intracerebroventricular morphine preconditioning on myocardial postischemia injury is mediated by adenosine receptor in spinal cord

作　　者：梅斌[1] 张野[1] 陆姚[1] 程新琦[2] 左友梅[1] 李锐[2] 高杉[3] 陈志武[3] 

机构地区：[1]安徽医科大学第二附属医院麻醉科,安徽合肥230601 [2]安徽医科大学第一附属医院麻醉科,安徽合肥230022 [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》2010年第8期1037-1041,共5页Chinese Pharmacological Bulletin

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

摘　　要：目的探讨脊髓腺苷受体在侧脑室吗啡预处理对大鼠心肌缺血/再灌注损伤的保护作用中的介导作用以及与心肌缺血/再灌注损伤所引起的炎症反应的关系。方法健康♂SD大鼠54只,随机分为假手术组(Sham组)、对照组(CON组)、吗啡预处理组(MPC)、腺苷体阻断剂茶碱(theophylline,THE)+吗啡预处理组(MPC+THE组)、另设茶碱自身对照组,除茶碱自身对照组(6只)外,其他每组12只。每组观察指标包括:平均动脉压(MAP)、心率(HR),计算平均动脉压和心率乘积(RPP);心肌缺血危险区(AAR)、梗死区(IS)的体积,心肌梗死面积以IS/AAR表示;免疫组化测定心肌组织细胞间黏附分子(ICAM-1)的表达水平。结果与CON组相比,MPC组的IS和IS/AAR均明显下降(P<0.01),MPC+THE组分别明显低于CON组(P<0.01),高于MPC组(P<0.01),THE自身对照组与CON组相比差异无显著性(P>0.05);CON组心肌中的ICAM-1的表达水平明显高于Sham组(P<0.01),MPC组心肌组织中的ICAM-1的表达水平明显低于CON组(P<0.01),而MPC+THE组心肌组织中的ICAM-1的表达水平高于MPC组(P<0.01),低于CON组(P<0.01)。结论侧脑室吗啡预处理可以上调大鼠脊髓腺苷受体的激动水平,后者通过抑制心肌缺血/再灌注损伤的炎症反应,部分介导了侧脑室吗啡预处理对大鼠心肌缺血/再灌注损伤的保护作用。Aim To investigate whether the protective effect of intracerebroventricular morphine preconditioning to myocardial is mediated by adenosine receptor in spinal cord,and the relationship with the inflammatory reaction of ischemia-reperfusion injury. Methods Rats with intrathecal and intracerebroventricular catheter placement were randomly assigned to 5 groups： Sham group,control group,MPC group,MPC ＋ THE group and THE group. Indicators to be observed were composed of MAP,HR and RPP （ MAP × HR） ; in-farct size （ IS） ,as a percentage of the area at risk,was determined by 2,3,5-triphenyltetrazolium staining,the volume of area at risk （ AAR） ,and the area of myocardial infarction,which was demonstrated by IS/AAR. And also the ICAM-1 expression in myocardium was determined by immunohistochemical method. Result Compared with the control group,the volume of IS and IS/AAR both declined in MPC group and MPC ＋ THE group （ P〈0. 01） ,but the volume of IS and IS/AAR of MPC ＋ THE group was higher than that of MPC group（ P〈0. 01） . There was no significant difference between THE group and the control group（ P〈0. 05） . ICAM-1 expression in myocardium of the control group was higher than those of Sham group,MPC group and MPC ＋ THE group. （ P〈0. 01） . Compared with MPC group,ICAM-1 expressed in myocardium of MPC ＋ THE group was much more（ P〈0. 01） . Conclusion Intracerebroventricular morphine can up-regulate the activation of adenosine receptor in spinal cord. The latter suppresses the inflammatory reaction of ischemia-reperfusion injury,and partly mediates the cardioprotective effect of intracerebroventricular morphine preconditioning this way.

关 键 词：吗啡 腺苷受体 心肌缺血/再灌注损伤 侧脑室 脊髓 炎症反应 

分 类 号：R-332[医药卫生] R322.11