右美托咪啶后处理对大鼠离体心脏缺血再灌注时线粒体损伤的影响

目的 探讨右美托咪啶后处理对大鼠离体心脏缺血再灌注时线粒体损伤的影响.方法 健康雌性Wistar大鼠,体重220～250 g,成功制备Langendorff离体灌注模型的40个心脏随机分为5组(n=8):缺血再灌注组(A组)、右美托咪啶10 nmol/L组(B组)、右美托咪啶100 nmol/L组(C组)、线粒体通透性转换孔开放剂苍术苷组(D组)及右美托咪啶联合苍术苷组(E组).离体心脏经K-H液平衡灌注20 min后,采用全心停灌40 min再灌注60 min的方法制备离体心脏缺血再灌注模型.于再灌注即刻B组、C组、D组和E组分别灌注含10 nmol/L右美托咪啶、100 nmol/L右美托咪啶、20μmol/L苍术苷、100 nmol/L右美托咪啶和20 μmol/L苍术苷的K-H液10 min.再灌注结束即刻取心尖组织,分离线粒体,测定SOD、Na+ -K+ -ATP酶、Ca2+-ATP酶活性和MDA和Ca2+含量.结果 与A组比较,B组和C组线粒体SOD、Na+ -K+ -ATP酶和Ca2+ -ATP酶活性升高,MDA和Ca2+含量降低(P＜0.05),D组和E组上述指标比较差异无统计学意义(P＞0.05)；与C组比较,D组和E组线粒体SOD、Na+-K+-ATP酶和Ca2+ -ATP酶活性降低,MDA和Ca2+含量升高(P＜0.05),B组上述指标比较差异无统计学意义(P＞0.05).结论 右美托咪啶后处理可减轻大鼠离体心脏缺血再灌注时的线粒体损伤,其机制可能与抑制线粒体通透性转换孔开放有关.

Effect of dexmedetomidine postconditioning on mitochondria injury during myocardial ischemiia-reperfusion in isolated rat hearts

Objective To investigate the effect of dexmedetomidine postconditioning on mitochondria injury during myocardial ischemia-reperfusion (I/R) in isolated rat hearts.Methods Healthy female Wistar rats weighing 220-250 g were anesthetized with intraperitoneal 3％ pentobarbital 50 mg/kg and heparin 500 U/kg.Their hearts were excised and perfused in a Langenorff apparatus with modified K-H solution saturated with 95％ O2-5％ C02 at 37 ℃.Forty isolated rat hearts were randomly divided into 5 groups( n =8 each): I/R group(group A),dexmedetomidine 10 nmol/L group ( group B),dexmedetomidine 100 nmol/L group ( group C ),atractyloside ( the mitochondrial permeability transitionpore (mPTP) opener) group (group D)and dexmedetomidine 100 nmol/L + atractyloside group(group E).Myocardial I/R injury was induced by 40 min of global ischemia followed by 60 min of reperfusion.10 nmol/L dexmedetonidine( group B),100 nmol/L dexmedetonidine (group C),20 μmol/L atractyloside(group D) or 100 nmol/L dexmedetomidine + 20 μmol/L atractyloside (group E) was added into K-H solution and perfused for 10 min at the beginning of reperfusion.The myocardial tissues were obtained and mitochondria were isolated at the end of reperfusion for determination of activity of SOD,Na+ -K+ -ATPase,and Ca2+ -ATPase and content of MDA and Ca2+.Results The activity of SOD,Na+ -K+ -ATPase and Ca2+ -ATPase was significantly higher and MDA and Ca2+ content lower in groups B and C than in group A( P ＜ 0.05).The activity of SOD,Na+ -K+ -ATPase and Ca2+ -ATPase was lower and MDA and Ca2+ content higher in groups E and D than in group C (P ＜ 0.05).There was no significant difference in activity of SOD,Na+ -K+ -ATPase and Ca2+ -ATPase and MDA and Ca2+ content between groups B and C,and between groups A and D( P ＞ 0.05).Conclusion Dexmedetomidine postconditioning can reduced mitochondria injury during myocardial I/R in isolated rat hearts through inhibiting of mPTP opening.