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目的本研究组在前期研究中证实雷帕霉素会减弱缺氧预处理对原代乳鼠心肌细胞的保护作用,本研究拟在整体心脏水平验证这一现象并探讨其机制。方法建立Langendorff大鼠离体心脏模型,分别测定并分析缺血再灌注(I/R)、缺氧预处理(HPC)、雷帕霉素干预后缺氧预处理(Rapa+HPC)三组的血流动力学指标,验证雷帕霉素对缺氧预处理心肌保护效应的影响,应用qRT-PCR技术测定HIF1α与mTOR的mRNA表达水平。结果 Rapa+HPC组再灌注后30min,60min心率与I/R组差异无统计学意义,Rapa+HPC组LVDP、dp/dt虽较HPC组降低(p<0.05),但仍高于I/R组。HPC组HIF1α mRNA与mTOR mRNA水平高于I/R(16.96±1.82 vs 1.01±0.13,p<0.05;1.99±0.32 vs 1.05±0.40,p<0.05),及Rapa+HPC组(1.56±0.36,p<0.05;0.63±0.06,p<0.05)。结论缺氧预处理早期可产生心肌保护作用,促进缺血再灌注后心脏功能的恢复。雷帕霉素会减弱缺氧预处理的心肌保护效应。这一早期保护作用涉及HIF1α与mTOR表达增加,雷帕霉素可通过HIF1α与mTOR在这一过程中的表达,减弱缺氧预处理早期心肌保护作用。
Objectives Our previous study confirmed that rapamycin attenuated the protective effect of hypoxia preconditioning on primary neonatal rat cardiomyocytes. This study aims to validate this phenomenon at the whole heart and to explore its mechanism. Methods The Langendorff rat model of isolated heart was established. The levels of I / R, HPC and Rapa + HPC were measured and analyzed in three groups Hemodynamic parameters to verify the effect of rapamycin on myocardial protection effect of hypoxic preconditioning. The mRNA expression levels of HIF-1α and mTOR were detected by qRT-PCR. Results Compared with I / R group, the LVDP and dp / dt of Rapa + HPC group were lower than those of HPC group (P <0.05) at 30min and 60min after reperfusion, but still higher than that of I / R group group. The levels of HIF1α mRNA and mTOR mRNA in HPC group were significantly higher than those in I / R group (16.96 ± 1.82 vs 1.01 ± 0.13, p <0.05; 1.99 ± 0.32 vs 1.05 ± 0.40, p <0.05) <0.05; 0.63 ± 0.06, p <0.05). Conclusions Early hypoxia preconditioning can produce myocardial protection and promote the recovery of cardiac function after ischemia reperfusion. Rapamycin attenuates cardioprotection by hypoxic preconditioning. This early protective effect involves an increase in the expression of HIF1α and mTOR. Rapamycin attenuates early myocardial protection by hypoxic preconditioning through the expression of HIF1α and mTOR in this process.