线粒体ATP敏感性钾通道在利多卡因预先给药减轻大鼠离体心脏缺血再灌注损伤中的作用

目的 评价线粒体ATP敏感性钾通道在利多卡因预先给药减轻大鼠离体心脏缺血再灌注损伤中的作用.方法 雌性成年Wistar大鼠,体重220～250 g,采用Langendorff装置建立大鼠离体心脏缺血再灌注模型.取模型制备成功的大鼠心脏24个,随机分为3组(n=8):缺血再灌注组(IR组)、利多卡因组(L组)和利多卡因+格列苯脲组(LG组).K-H液平衡灌注10 min后,C组、L组和LG组分别灌注K-H液、含2.5 mg/L利多卡因的K-H液、含2.5 mg/L利多卡因+10μmol/L格列苯脲(线粒体ATP敏感性钾通道阻断剂)的K-H液20 min,然后缺血30 min,再灌注60 min.分别于平衡灌注末(T0)、再灌注15 min(T1)、30 min(T2)、45 min(T3)和60 min(T4)时,记录HR、左心室发展压(LVDP)、左心室内压最大上升速率(+dp/dtmax)和左心室内压最大下降速率(-dp/dtmax).于T0和T4时,收集冠状动脉流出液,测定乳酸脱氢酶(LDH)和肌酸激酶(CK)的活性.于T4时取心尖周围心肌组织,测定Na+-K+-ATP酶和SOD的活性、MDA和Ca2+的含量.结果 与IR组比较,L组HR、LVDP、+dp/dtmax和-dp/dtmax升高,CK和LDH的活性降低,心肌Na+-K+-ATP酶和SOD的活性升高,Ca2+和MDA的含量降低(P＜0.05),LG组上述各指标差异无统计学意义(P＞0.05).与L组比较,LG组HR、LVDP、+dp/dtmax和-dp/dmax.降低,CK和LDH的活性升高,心肌Na+-K+-ATP酶和SOD的活性降低,Ca2+和MDA的含量升高(P＜0.05).结论 利多卡因预先给药减轻大鼠离体心脏缺血再灌注损伤与促进线粒体ATP敏感性钾通道的开放有关.

Role of mitochondrial ATP-sensitive potassium channels in attenuation of ischemia-reperfusion injury by lidocaine pretreatment in isolated rat heart

Objective To investigate the role of mitochondrial ATP-sensitive potassium(mito-KATP)channels in attenuation of ischemia-reperfusion(I/R)injury by lidocaine pretreatment in the isolated rat heart.Methods Adult female Wistar rats weighing 220-250 g were anesthetized with intraperitoneal 3% pentobarbital 35 mg/kg.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95%O2-5%CO2 at 37 ℃.Twenty-four isolated rat hearts with I/R injury were randomly divided into 3 groups(n = 8 each):group I/R,lidocaine group(group L)and lidocaine + glibenclamide group(group LG).After 10 min of equilibration,group C,L and LG received 20 min of perfusion with K-H solution,K-H solution containing lidocaine 2.5 mg/L and K-H solution containing lidocaine 2.5 mg/L + glibenclamide(a blocker of mito-KATP channels)10 μmol/L,respectively,then subjected to 30 min of ischemia followed by 60 min of reperfusion.HR,left ventricular developed pressure(LVDP),+ dp/dtmax and - dp/dtmax were recorded at the end of equilibration(T0)and at 15,30,45 and 60 min of reperfusion(T1-4).Coronary effluent was collected at T0 and T4 for determination of lactate dehydrogenase(LDH)and creatine kinase(CK)activities.Myocardial tissues were obtained from cardiac apex at T4 for determination of Na+ -K+ -ATPase and SOD activities and MDA and Ca2+ contents.Results Compared with group I/R,HR,LVDP,+ dp/dtmax and - dp/dtmax were significantly increased,CK and LHD activities were decreased,Na+ -K+-ATPase and SOD activities were increased,and MDA and Ca2+ contents were decreased in group L(P ＜0.05).Compared with group L,HR,LVDP,+ dp/dtmax and -dp/dtmax were significantly decreased,CK and LHD activities were increased,Na+ -K+ -ATPase and SOD activities were decreased,and MDA and Ca2+ contents were increased in group LG(P＜0.05).Conclusion The mechanism by which lidocaine pretreatment attenuates I/R injury to the isolated rat heart is related to mito-KATP channel opening.