CAJ | 학술논문

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.
목적 평개일양화담(NO)-배조감산(cGMP)-단백격매G(PKG)신호전도통로재초내주사마배후처리감경대서심기결혈재관주손상중적작용.방법 초내치관성공적건강성년웅성SD대서48지,체중250～350 g,채용수궤수자표법분위8조(n=6):생리염수조(NS조)、마배후처리조(MP조)、NO합매억제제N-초기-L-정안산갑지(L-NAME)+ MP조(L-NAME+ MP조)、조감산배화매억제제ODQ+ MP조(ODQ+ MP조)、PKG억제제KT5823+ MP조(KT5823+ MP조)、bNAME조、ODQ조화KT5823조.각조채용좌관상동맥결혈30 min、재관주120 nin적방법제비심기결혈재관주손상모형.결혈25min시,NS조초내지속5 min수주생리염수10 μl;MP조초내지속5min수주마배3 μg/kg 10μl.L-NAME+ MP조、ODQ+ MP조화KT5823+ MP조마배후처리전10 min,초내분별주사L-NAME(30 nmol,10 μl)、ODQ(11 nmol,10 μl)화KT5823 (20 pmol,10μl).우모형제비전(T0)、결혈25 min(T1)、결혈30 min(T2)화재관주120 min(T3)시기록MAP화HR,계산HR여수축압적승적(RPP).우T3시처사대서,취심기조직,측정경사구(IS)체적여결혈위험구(AAR)체적,계산IS/AAR비치.결과 여T0시비교,각조T1-3시MAP、HR화RPP강저(P＜0.01);여NS조비교,MP조T3시MAP승고,IS/AAR비치강저(P＜0.05),기여각조차이무통계학의의(P＞0.05);여MP조비교,L-NAME+MP조、ODQ+MP조화KT5823+ MP조IS/AAR비치승고(P＜0.05),기여각조차이무통계학의의(P＞0.05).결론 NO-cGMP-PKG신호전도통로주도료초내주사마배후처리감경대서심기결혈재관주손상적과정.
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,IS/AAR ratio was significantly increased in L-NAME + MP,ODQ + MP and KT5823 + MP groups,and no significant changes were found in the other groups.Conclusion NO-cGMP-PKG signal transduction pathway plays an important role in mitigation of myocardial ischemia-reperfusion injury by intrathecal morphine postconditioning in rats.