中枢阿片受体介导鞘内注射吗啡对大鼠缺血后心肌的保护作用

Cardioprotective effect of intrathecal morphine on ischemia-reperfusion injury heart mediated by opioid receptors in central nervous system

目的探讨鞘内注射吗啡预处理对缺血/再灌注心肌的影响及中枢神经系统阿片受体在其中的作用。方法建立大鼠鞘内注射和心脏缺血/再灌注损伤的动物模型。分为对照组(NS)和鞘内注射吗啡预处理组(M),M组分4个剂量组(M1,10μg·kg-1;M2,1μg·kg-1;M3,0.1μg·kg-1;M4,0.01μg·kg-1)。鞘内注射吗啡的方法是分别在缺血/再灌注前30 min鞘内注射吗啡5 min,间隔5 min共3次。在M2组鞘内注射吗啡前鞘内注射3种选择性阿片受体拮抗剂Naltrindole(NTD,δ阿片受体阻断剂,15 nmol(nM),NTD+M2组)、nor-Binaltorphimine(nor-BNI,κ阿片受体阻断剂,15 nmol.L-1,nor-BNI+M2组)和CTOP(μ阿片受体阻断剂,15 nM,CTOP+M2组)。观察指标包括:平均动脉压(MAP)、心率(HR)、计算平均动脉压和心率乘积(RPP);缺血危险区(AAR)、梗死区(IS)的体积、心肌梗死面积以IS/AAR来表示。结果M1组、M2组和M3组的IS/AAR均低于NS组(P<0.05,P<0.01),M4组与NS组的IS/AAR相似(P>0.05);NTD+M2组、nor-BNI+M2组和CTOP+M2组与自身对照组(NS+NTD组,NS+nor-BNI组和NS+CTOP组)及NS组相比差异无显著性(P>0.05),而均高于M2组(P<0.05,P<0.01)。各组在各时点的MAP、HR和RPP差异无显著性(P>0.05)。结论鞘内注射吗啡对在体大鼠心肌缺血/再灌注损伤有保护作用,中枢神经系统的δ,κ和μ三种阿片受体都参与介导了其保护作用。

Aim To investigate the effect of intrathecal morphine against ischemia-reperfusion injury in intanct rat heart and the mechanism of the central nervous system opioid receptor. Methods Rats with intrathecal catheter placement were subject to 30 min ischemia and 120 min reperfusion and randomly assigned to 11 groups：control （ NS, saline vehicle） ; intrathecal morphine （M, according to the dosage of intrathecal morphine,M was assigned to four groups, M1,10 μg · kg^-1;M2,1 μg · kg^-1;M3,0. 1 μg · kg^-1;M4,0.01 μg · kg^-1 ）, M2 ＋ NTD, M2 ＋ nor-BNI and M2 ＋ CTOP （three kinds of selective opioid receptor antagonist（ 15 nmol） intrathecal 10 min before intrathecal morphine）, and itself control （ NS ＋ NTD, NS ＋ nor-BNI and NS ＋ CTOP）. Infarct size （IS） and the percentage of the area at risk （ AAR）, were determined by triphenyltetrazolium （ TTC ） staining. Results Intrathecal injection of morphine （0. 1,1,10 μg · kg^-1） significantly reduced the IS/AAR compared to NS group. δ, Kand μ opiate receptor antagonists NTD, nor-Binaltor- phimine and CTOP reserved the cardioprotective effect of intrathecal morphine on ischemia-reperfusion injury. Conclusions The cardioprotective effect of intrathecal morphine was reversed by all three opioid receptor an- tagonists ： nahrindole, nor-Binaltorphimine and CTOP, and it suggested that this effect was mediated via δ, K and μ, three kinds of opioid receptors of central nervous system.