NO-cGMP-PKG信号转导通路在鞘内注射吗啡后处理减轻大鼠心肌缺血再灌注损伤中的作用  

Role of NO-cGMP-PKG signal transduction pathway in mitigation of myocardial ischemia-reperfusion injury by intrathecal morphine postconditioning in rats

作　　者：胡军[1] 蒋玲玲[1] 何淑芳[1] 金世云[1] 何伟天 张野[1] 

机构地区：[1]安徽医科大学第二附属医院麻醉科,合肥市230601

出　　处：《中华麻醉学杂志》2014年第5期555-558,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金青年科学基金（81200089）

摘　　要：目的 评价一氧化氮（NO）-环鸟苷酸（cGMP）-蛋白激酶G（PKG）信号转导通路在鞘内注射吗啡后处理减轻大鼠心肌缺血再灌注损伤中的作用.方法 鞘内置管成功的健康成年雄性SD大鼠48只,体重250～350 g,采用随机数字表法分为8组（n=6）：生理盐水组（NS组）、吗啡后处理组（MP组）、NO合酶抑制剂N-硝基-L-精氨酸甲酯（L-NAME）＋ MP组（L-NAME＋ MP组）、鸟苷酸环化酶抑制剂ODQ＋ MP组（ODQ＋ MP组）、PKG抑制剂KT5823＋ MP组（KT5823＋ MP组）、bNAME组、ODQ组和KT5823组.各组采用左冠状动脉缺血30 min、再灌注120 nin的方法制备心肌缺血再灌注损伤模型.缺血25min时,NS组鞘内持续5 min输注生理盐水10 μl;MP组鞘内持续5min输注吗啡3 μg/kg 10μl.L-NAME＋ MP组、ODQ＋ MP组和KT5823＋ MP组吗啡后处理前10 min,鞘内分别注射L-NAME（30 nmol,10 μl）、ODQ（11 nmol,10 μl）和KT5823 （20 pmol,10μl）.于模型制备前（T0）、缺血25 min（T1）、缺血30 min（T2）和再灌注120 min（T3）时记录MAP和HR,计算HR与收缩压的乘积（RPP）.于T3时处死大鼠,取心肌组织,测定梗死区（IS）体积与缺血危险区（AAR）体积,计算IS/AAR比值.结果 与T0时比较,各组T1-3时MAP、HR和RPP降低（P＜0.01）;与NS组比较,MP组T3时MAP升高,IS/AAR比值降低（P＜0.05）,其余各组差异无统计学意义（P＞0.05）;与MP组比较,L-NAME＋MP组、ODQ＋MP组和KT5823＋ MP组IS/AAR比值升高（P＜0.05）,其余各组差异无统计学意义（P＞0.05）.结论 NO-cGMP-PKG信号转导通路主导了鞘内注射吗啡后处理减轻大鼠心肌缺血再灌注损伤的过程.Objective To evaluate the role of nitric oxide （NO）-cyclic guanosine monophosphate （cGMP）-protein kinase G （PKG） signal transduction pathway in mitigation of myocardial ischemia-reperfusion injury by intrathecal morphine postconditioning in rats.Methods Forty-eight male Sprague-Dawley rats in which intrathecal catheters were successfully placed without complications,weighing 250-350 g,were randomly assigned into 8 groups （n =6 each）：normal saline group （NS group）,morphine postconditioning group （Mp group）,1-NG-nitroarginine methyl ester （L-NAME,NO synthase inhibitor） ＋ morphine postconditioning group （L-NAME ＋ MP group）,ODQ （guanylate cyclase inhibitor） ＋ morphine postconditioning group （ODQ ＋ MP group）,KT5823 （PKG inhibitor） ＋ morphine postconditioning group （KT5823 ＋ MP group）,L-NAME group,ODQ group and KT5823 group.Myocardial ischemia was induced by 30 min of occlusion of anterior descending branch of left coronary artery followed by 2 h of reperfusion.At 25 rin of ischemia,normal saline 10 μl was intrathecally infused over 5 min in group NS,and morphine （3 μg/kg,10 μl） was intrathecally infused over 5 min in group MP.L-NAME （30 nmol,10 μl）,ODQ （11 nmol,10 μl） and KT5823 （20 pmol,10 μl） were intrathecally injected at 10 rin before morphine postconditioning in L-NAME ＋ MP,ODQ ＋ MP and KT5823 ＋ MP groups,respectively.Before myocardial ischemia （T0）,at 25 and 30 min of ischemia （T1-2）,and at 120 min of reperfusion （T3）,MAP and HR were recorded,and rate-pressure product （RPP） was calculated.The rats were sacrificed at T3,and myocardial specimens were obtained for determination of myocardial infarct size as a percentage of area at risk （IS/AAR）.Results MAP,HR and RPP were significantly lower at T1-3 than at T0 in each group.Compared with group NS,MAP was significantly increased at T3,and IS/AAR ratio was decreased in MP group,and no significant changes were found in the other groups.Compared with group MP,I

关 键 词：一氧化氮 环GMP 蛋白激酶类 注射 脊髓 吗啡 心肌再灌注损伤 

分 类 号：R542.2[医药卫生—心血管疾病]