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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 observe the protective effect of opioid μ receptor agonist-remifentanil on myocardial ischemia-reperfusion injury in isolated rat hearts and to explore its molecular mechanism of p38MAPK signaling pathway and its anti-ischemic-reperfusion injury Possible Mechanism of Myocardial Apoptosis. Methods Forty SD male rats weighing 220-250 g were randomly divided into 5 groups (n = 8): ischemia reperfusion group (C), 100 μg / L remifentanil postconditioning group (R), 100 μg / L Remifentanil treatment + 1μmol / L naloxone group (R + N), 100μg / L remifentanil treatment + 10μmol / L nytoindole group (R + NTI), 100μg / Taurine aftertreatment + 5 μmol / L SB203580 group (R + SB). Establishment of Langendorff rat isolated heart perfusion model. Krebs-Henseleit buffer (KHS) was equilibrated perfused the isolated beating heart for 20 min, followed by experimental ischemia for 30 min, followed by perfusion of the corresponding perfusate for 60 min. Group C was infused with blank KBS for 60 min, and the remaining four groups were perfused with KHS containing the corresponding reagents for 60 min. The ventricular mechanical parameters HR and LVDP were measured at 5 min before ischemia, 30 min after reperfusion and 60 min after reperfusion. After 60 min of reperfusion, myocardial apoptosis was detected by Tune1 method in left ventricular myocardium. Results Compared with group C, HR group, LVDP group and cardiomyocyte apoptosis rate of R group were significantly decreased at 30min and 60min after reperfusion (P <0.05). There was no significant difference between other groups (P> 0.05). Conclusion remifentanil postconditioning can significantly reduce the impact of ischemia-reperfusion on cardiac function, inhibit myocardial ischemia-reperfusion-induced apoptosis in vitro, delta opioid receptor antagonist natadinol can be partially shielded from the Swiss Cardioprotective effects of fentanyl aftertreatment suggest that this protective effect is partly related to remifentanil agonist delta opiate receptors. p38MAPK molecular signaling mechanism is involved in opioid receptor-mediated myocardial protection and is an important signal transduction pathway to reduce myocardial cell apoptosis during ischemia-reperfusion.