NO/cGMP信号通路在鞘内吗啡预处理减轻大鼠心肌缺血/再灌注损伤中的作用  

Role of NO /cGMP in the cardioprotective effects of intrathecal morphine preconditioning against myocardial ischemia-reperfusion injury in rats

作　　者：胡军[1] 张野[1] 陆姚 蒋玲玲[1] 何淑芳[1] 

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]第三附属医院麻醉科,安徽合肥230061

出　　处：《中国药理学通报》2014年第6期829-833,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助课题(No 81100105,81200089);安徽省科技厅年度重点项目(No 1301043030)

摘　　要：目的探讨NO/cGMP信号通路在鞘内吗啡预处理减轻大鼠心肌缺血/再灌注损伤中的作用。方法大鼠建立鞘内置管的模型。随机分为9组,每组6只:SHAM组(假手术组)、CON组(对照组,生理盐水)、ITMP组(鞘内吗啡预处理,3μg·kg-1)、L-NAME+ITMP组(一氧化氮合酶阻断剂+鞘内吗啡预处理)、ODQ+ITMP组(鸟苷酸环化酶阻断剂+鞘内吗啡预处理)、KT5823+ITMP组(蛋白激酶G阻断剂+鞘内吗啡预处理)、L-NAME组、ODQ组、KT5823组。ITMP组于心脏缺血前,鞘内注射吗啡10μl 5 min,间断5 min,重复3次;CON组以相同的方式注射生理盐水;L-NAME+ITMP组、ODQ+ITMP组、KT5823+ITMP组分别于吗啡预处理前10 min鞘内注射L-NAME(30 nmol,10μl)、ODQ(11nmol,10μl)、KT5823(20 pmol,10μl);L-NAME组、ODQ组、KT5823组为阻断剂自身对照组。除SHAM组行假手术操作不做其他处理,其余各组大鼠均行左冠状动脉缺血30 min,再灌注120 min诱导心肌缺血/再灌注损伤。观察指标包括:血流动力学指标;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组相比,ITMP组的IS和IS/AAR均明显下降(P<0.01);与ITMP组比较,L-NAME+ITMP组、ODQ+ITMP组、KT5823+ITMP组的IS和IS/AAR均升高(P<0.01)。与SHAM组比较各组MAP和RPP在缺血30 min降低(P<0.05),与基础值比较,除SHAM组外,其余各组MAP和RPP在缺血30 min降低(P<0.05)。结论 NO/cGMP的信号通路可能参与介导鞘内吗啡预处理,对大鼠心肌缺血/再灌注损伤的保护作用。Aim To investigate the role of NO/cGMP in the cardioprotective effects of intrathecal morphine preconditioning against myocardial ischemia-reperfu-sion injury in rats. Method 54 Male Sprague-Dawley Rats were used to establish the model of intrathecal catheter placement. The rats were randomly assigned to 9 groups. SHAM （sham group）, CON （control, sa-line） , ITMP （ intrathecal morphine preconditioning, 3μg·kg-1 ） , L-NAME＋ITMP （ NO synthetase inhibi-tor,L-NAME ） , ODQ ＋ ITMP （ guanylate cyclase in-hibitor, ODQ ） , KT5823 ＋ ITMP （ PKG inhibitor, KT5823）,L-NAME,ODQ,KT5823,6ratsineach group. ITMP were produced by three cycles of 5 min intrathecal injection of morphine and 5 min intermis-sion before myocardial ischemia, CON were achieved by intrathecal injection of saline in the same way, L-NAME＋ITMP, ODQ ＋ITMP, KT5823 ＋ITMP were prepared by intrathecally administering L-NAME （ 30 nmol）, ODQ（11 nmol） and KT5823（20 pmol） 10 minutes prior to ITMP respectively, L-NAME, ODQ, KT5823 worked as the control of inhibitors themselves respectively without ITMP. Subsequently, all rats were subjected to 30 min of left coronary artery occlusion followed by 2 h of reperfusion except the SHAM group. Myocardial infarct size, as a percentage of the AAR, was determined by 2 , 3 , 5-triphenyltetrazolium stai-ning. Results Compared with CON, the volumes of IS and IS/AAR were reduced in ITMP （ P 〈0.01 ）;the protective effects of ITMP were abolished by pre-treatment with L-NAME, ODQ and KT5823 （ P 〈0.01 ）;Conclusions NO/cGMP might be involved in the cardioprotective effect of intrathecal morphine preconditioning against myocardial ischemia and reperfu-sion injury in rats.

关 键 词：吗啡 鞘内注射 缺血 再灌注损伤 阿片样受体 一氧化氮 环GMP 环GMP依赖性蛋白激酶类 

分 类 号：R332[医药卫生—人体生理学] R322.11[医药卫生—基础医学]