CGRP、K_(ATP)通道和脊神经在鞘内注射吗啡预处理减轻大鼠心肌缺血后损伤中的作用  

Role of calcitonin gene related peptide,ATP sensitive potassium channel and spinal nerve in the protective effects of intrathecal morphine preconditioning against myocardial postischemia injury in rats

作　　者：陆姚 张野[2] 王苑[3] 李锐[4] 陈志武[5] 

机构地区：[1]安徽医科大学第三附属医院麻醉科,安徽合肥230061 [2]安徽医科大学第二附属医院麻醉科,安徽合肥230601 [3]香港大学麻醉系,香港999077 [4]安徽医科大学第一附属医院麻醉科,安徽合肥230022 [5]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7期886-890,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：目的探讨降钙素基因相关肽(CGRP)、ATP敏感性钾离子通道(KATP通道)和脊神经在鞘内注射吗啡预处理对在体大鼠心肌缺血/再灌注损伤中的保护作用。方法♂SD大鼠60只,建立鞘内置管和心肌缺血/再灌注损伤模型,随机分为10组,每组6只:对照组(CON,生理盐水)、二甲亚砜组(DMSO,GLI的溶剂)、CGRP8-37组(CGRP受体阻滞剂,3nmol.kg-1)、格列苯脲组(GLI,KATP通道阻滞剂,0.3 mg.kg-1)、利多卡因组(LID,1%盐酸利多卡因10μl)、鞘内注射吗啡预处理组(MPC,3×1μg.kg-1)、CGRP8-37+MPC组、GLI+MPC组、LID+MPC组、GLI+LID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。结果与CON组比较,MPC组、LID组、LID+MPC组和GLI+LID组的IS和IS/AAR均明显下降(P<0.05,P<0.01);与MPC组比较,CGRP8-37+MPC组、GLI+MPC组和LID+MPC组的IS和IS/AAR均明显增加(P<0.01)。结论外周CGRP的释放、KATP通道和脊神经可能参与了鞘内注射吗啡预处理减轻大鼠心肌缺血后损伤的作用。Aim To investigate the role of calcitonin gene related peptide（CGRP）,ATP sensitive potassium channel（KATP）and spinal nerve in the protective effect of intrathecal morphine preconditioning against myocardial postischemia injury in rats.Methods Rats were established intrathecal catheter placement and myocardial ischemia reperfusion models were randomly assigned to 10 groups：control group（CON）;intravenous dimethylsulfoxide group（DMSO）;intravenous CGRP8-37 group（CGRP8-37,a selective CGRP receptor antagonist,3 nmol·kg-1）;intravenous glibenclamide group（GLI,a non-selective KATP channel inhibitor,0.3 mg·kg-1）;intrathecal 10 μl of 1% lidocaine group（LID）;intrathecal 3×1 μg·kg-1 morphine preconditioning group（MPC）;intravenous 3 nmol·kg-1 CGRP8-37＋MPC group（CGRP8-37＋MPC）;intravenous 0.3 mg·kg-1 GLI＋MPC group（GLI＋MPC）;intravenous 0.3 mg·kg-1 GLI＋LID group（GLI＋LID）.Indicators to be observed were MAP,HR and RPP（MAP×HR）,the volume of area at risk（AAR）and infarct size（IS）,and the area of myocardial infarction,which was demonstrated by IS/AAR.Results Compared to CON group,the volume of IS and IS/AAR was reduced in MPC,LID,LID＋MPC and GLI＋LID group（P〈0.01,P〈0.05）.Compared to MPC group,the volume of IS and IS/AAR in CGRP8-37＋MPC,GLI＋MPC and LID＋MPC group was raised significantly（P〈0.01）.Conclusion CGRP release,KATP channel and spinal nerve are involved in the protective effect of intrathecal morphine preconditioning against myocardial postischemia injury.

关 键 词：吗啡 鞘内注射 心肌缺血/再灌注损伤 缺血预处理 降钙素基因相关肽 ATP敏感性钾离子通道 

分 类 号：R-332[医药卫生] R322.11