线粒体KATP在吡那地尔预处理后失血性休克大鼠组织血流灌注和线粒体功能保护效应中的作用

Role of mitochondrial KATP channel in pinacidil pretreatment-induced protective effect on blood flow and mitochondrial function of hemorrhagic shock rats

目的观察吡那地尔(pinacidil)预处理对失血性休克大鼠血流灌注和线粒体功能的保护效应,及其与线粒体ATP激活钾通道[adenosine triphosphate(ATP)-activated potassium channels,KATP]的关系。方法 Wistar大鼠60只,随机数字表法分为:正常对照组、休克组、乳酸林格液(LR)复苏组、吡那地尔预处理组、5-HD组、格列本脲组,通过微血管张力测定技术、激光多普勒技术以及氧浓度测定技术,观察吡那地尔预处理(25μg/kg,腹腔注射)对失血性休克和复苏过程中血管反应性和钙敏感性、脑、肝、肾重要器官的血流灌注和线粒体功能的保护作用,以及线粒体KATP通道关闭剂5-HD和格列本脲对其抑制作用。结果与LR复苏组相比,吡那地尔预处理可显著增高肠系膜上动脉(SMA)对去甲肾上腺素(NE)和Ca2+的最大收缩力(Emax)以及NE的升压效应,使其分别增高24.95%、15.48%和18.53%(P<0.01),增加脑、肝、肾血流量,恢复肝、肾的线粒体呼吸控制率(respiration control ratio,RCR)和Na+-K+-ATP酶活性(P<0.01)。5-HD和格列本脲均可显著抑制吡那地尔预处理的上述作用(P<0.01)。结论吡那地尔预处理通过开放线粒体KATP通道,改善失血性休克大鼠血管收缩反应,从而保护器官血流灌注和线粒体功能。

Objective To investigate pinacidil pretreatment-induced protection on blood flow and mitochondrial function of hemorrhagic shock rats and role of mitochondrial KATP channel in this process.Methods Sixty Wistar rats（200-230 g,male and female in half） were randomly divided into six groups including sham operation group,shock group,lactated ringer＇s solution（LR） resuscitation group,pinacidil pretreatment group（25 μg/kg,intraperitoneal injection）,5-hydroxydecanoate（5-HD） group and glibenclamide group.Microvascular tension measurement technique,laser-Doppler technique and oxygen concentration determination method were applied to observe the protective effect of pinacidil pretreatment on vascular reactivity,calcium sensitivity,blood flow and mitochondrial function in the brain,liver and kidney,and the inhibitory effects of mitochondrial KATP channel blocker 5-HD and glibenclamide.Results As compared with LR resuscitation group,pinacidil pretreatment significantly increased the maximum contraction（Emax） of superior mesenteric artery（SMA） for norepinephrine（NE） and Ca2＋,and raised the presser effect of NE by 24.95%,15.48% and 18.53%,respectively（P〈0.01）;Pinacidil pretreatment also improved blood flow of the brain,liver and kidney,mitochondrial respiration control ratio（RCR） and activity of Na^＋-K^＋-ATPase（P〈0.01）.All these effects could be significantly blocked by 5-HD and glibenclamide（P〈0.01）.Conclusion Pinacidil pretreatment-induced effect protects blood flow and mitochondrial function of hemorrhagic shock rats through mitochondrial KATP channel.