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目的研究urocortin(UCN)对缺血再灌注诱导的心肌细胞自噬的影响,探讨UCN的心肌保护机制。方法构建大鼠在体心脏缺血再灌注损伤和离体新生大鼠心肌细胞的缺氧复氧模型,进行缺血/缺氧1h再灌注/复氧2h的损伤,在缺血/缺氧前1h给予UCN预处理;在再灌注/复氧2h后观察UCN对缺血再灌注/缺氧复氧诱导的心肌损伤、细胞自噬和自噬相关基因表达的影响。结果 UCN预处理可以显著降低缺血再灌注损伤导致的心肌损害,使梗死面积降低,血清肌酸激酶(CK)、乳酸脱氢酶(LDH)降低;增加缺氧复氧离体心肌细胞活力、减少培养上清的LDH水平。与上述心肌保护作用相伴随的是UCN预处理还能抑制缺氧复氧导致的心肌细胞自噬,使LC3BⅡ/LC3BⅠ的比值显著降低,并且抑制自噬相关基因Beclin1、Bnip3的mRNA表达。结论 UCN可以抑制缺血再灌注诱导的心肌细胞自噬,可能在抗缺血再灌注损伤中起重要作用。
Objective To investigate the effect of urocortin (UCN) on autophagy induced by ischemia-reperfusion in cardiomyocytes and to explore the protective mechanism of UCN on myocardium. Methods The model of hypoxia-reoxygenation injury was established in both ischemia-reperfusion injury and neonatal rat cardiomyocytes in vivo. The ischemia / hypoxia 1h reperfusion / reoxygenation 2h injury was performed. Before ischemia / hypoxia 1h before UCN preconditioning. After 2h reperfusion / reoxygenation, the effects of UCN on myocardial injury, autophagy and autophagy-related gene expression induced by ischemia / reperfusion / hypoxia and reoxygenation were observed. Results UCN preconditioning could significantly reduce myocardial damage caused by ischemia-reperfusion injury, reduce infarct size, decrease serum creatine kinase (CK) and lactate dehydrogenase (LDH), increase myocardial viability in hypoxia- Reduce LDH levels in culture supernatants. Concurrently with the myocardial protection, UCN preconditioning can also inhibit cardiac myocyte autophagy induced by hypoxia-reoxygenation, significantly reduce the ratio of LC3BⅡ / LC3BⅠ, and inhibit the mRNA expression of autophagy-related genes Beclin1 and Bnip3. Conclusion UCN can inhibit ischemia-reperfusion-induced cardiomyocyte autophagy and may play an important role in anti-ischemia-reperfusion injury.