瑞芬太尼后处理对大鼠离体缺血再灌注心肌凋亡的影响-P38MAPK信号转导系统的意义  

Protective effect of remifentanil postcondition on myocardium apoptosis against ischemia/reperfusion injury in isolated rats:Role of p38 mitogen-activated protein kinases pathway

作　　者：宋彩霞[1] 吕国义[2] 邓迺封[2] 

机构地区：[1]天津医科大学研究生院 [2]天津医科大学第二医院

出　　处：《齐齐哈尔医学院学报》2012年第17期2293-2295,共3页Journal of Qiqihar Medical University

摘　　要：目的观察阿片μ受体激动剂-瑞芬太尼后处理对离体大鼠心肌缺血再灌注损伤的保护作用,探讨其抗缺血再灌注损伤过程中,p38MAPK分子信号通路及其介导的心肌凋亡效应的可能机制。方法 40只SD雄性大鼠体重220～250g,随机分为5组(n=8),即:缺血再灌注组(C)、100μg/L瑞芬太尼后处理组(R)、100μg/L瑞芬太尼后处理+1μmol/L纳洛酮组(R+N)、100μg/L瑞芬太尼后处理+10μmol/L纳曲吲哚组(R+NTI)、100μg/L瑞芬太尼后处理+5μmol/L SB203580组(R+SB)。建立Langendorff大鼠离体心脏灌注模型。Krebs-Henseleit缓冲液(KHS)平衡灌注自主跳动的离体心脏20min,继之30min实验性缺血,再灌注相应灌流液60min。C组灌注空白KBS60min,其余四组分别灌注含相应试剂的KHS 60min。分别测定缺血前5min,再灌注30min,再灌注60min的心室力学指标HR和LVDP。取再灌注60min后左室心肌组织用Tune1法检测心肌细胞凋亡情况。结果与C组比较,R组再灌注30min、60min心室力学指标HR和LVDP以及心肌细胞凋亡率明显降低(P<0.05),其余各组间差异无显著性(P>0.05)。结论瑞芬太尼后处理可明显减轻缺血再灌注对心功能的影响,抑制离体大鼠心肌缺血再灌注造成的细胞凋亡,δ阿片受体拮抗剂纳曲吲哚可部分屏蔽瑞芬太尼后处理的心肌保护作用,表明该保护作用部分与瑞芬太尼激动δ阿片受体有关。p38MAPK分子信号机制参与了阿片受体介导的心肌保护作用,是减少缺血再灌注心肌细胞凋亡重要的信号转导通路。Objective To investigate the protective effect of remifentanilpostconditing on myocar- dium apoptosis against ischemia-reperfusion injury in isolated rats and the role of p38 mitogen--activa- ted protein kinases pathway. Methods 40 Female SD rats weighing 220-250g, were randomly divided into 5 groups （8 in each）. Ischemia-- reperfusion（C） group, ischemic postconditioning （P） group, Ref 100μg/L （R） group, Ref 100μg/L and naloxone 1μmol/L（R＋N） group, Ref 100μg/L and natrindole 10μmol/L（R-q-NTI） group, postconditioning and naloxone 10μmol/L（P＋N） group, Ref 100μg/L and SB203580 5μmol/L（R＋SB） group. The isolated hearts were mounted on modified Langendorff appara- tus. Each group were perfused with cor for 20 min respectively prior to ischemia. Then, the heart was subjected to no--flow global normothermic ischemia for 30min, after that, reperfused with the corre- sponding solution for 60rain. Heart rate （HR） and left ventricular developed pressure （LVDP） Hemody- namic parameters were recorded at 5th rain before ischemia as baseline, 30th rain, and 60th rain again post-reperfusion. The number of myocardium apoptosis was countered by TUNEL staining method. Results The HR and LVDP at 30 rain and 60 rain of reperfusion in group R were higher than that in group C （P 〈 0.05）, the others were no statistical different （P 〉 0.05）. TUNEL staining：The number of myocardium apoptosis was significantly lower in group R than that in group C;however, there were no significant differences among other groups （P 〉 0.05）. Conclusions Remifentanil postconditioning can protect isolated rats＇ heart against ischemia-reperfusion injury and decrease the number of myocardium apoptosis. The mechanism is possibly related to the molecular pathway of p38MAPK through the opioid recepoters.

关 键 词：瑞芬太尼 阿片受体 丝裂原活化蛋白激酶P38 缺血后处理 凋亡 

分 类 号：R542.2[医药卫生—心血管疾病]