大蒜素预处理对乳鼠心肌细胞缺氧复氧延迟保护作用的研究

Delayed cardioprotective effect of Allitridum on neonatal rat myocardiocytes subjected to hypoxia/reoxygenation (H/R)

目的 :研究大蒜素预处理对乳鼠心肌细胞缺氧复氧的延迟保护作用及其机制。方法 :采用细胞存活率、乳酸脱氢酶 (LDH)活性、丙二醛 (MDA)含量作为心肌细胞受损指标。观察终浓度分别为 5、1 0、2 0、5 0 μg/ml的大蒜素预处理以及预处理 1 2、2 4、3 6h后对乳鼠心肌细胞缺氧复氧损伤的影响 ,并观察蛋白激酶C(PKC)抑制剂H 7、丝裂素激活蛋白激酶 (MAPKs)抑制剂PD 980 5 9对大蒜素预处理的作用。结果 :大蒜素能提高细胞存活率 ,减少LDH漏出和MDA生成。其中 2 0 μg/ml浓度作用较强。大蒜素预处理 1 2h后即产生延迟保护作用 ,2 4h最强 ,3 6h消失。H 7、PD 980 5 9能够完全清除大蒜素预处理的心肌保护作用。结论 :大蒜素可以模拟缺血预处理延迟保护作用 ,其机制涉及PKC及MAPKs信号途径。

Objective:To investigate the delayed cardioprotective effect of Allitridum preconditioning on cultured neonatal rat myocardiocytes subjected to H/R and its mechanisms. Methods: Cultured neonatal rat cardiomyoctytes were preconditioned using Allitridum at different concentrations (5?10?20?50 μg/ml) and different time points. Cell viability, lactate dehydrogenase (LDH) release and malondialdehyde (MDA) formation were measured to determine the protective effects against H/R injury. Results: Increased cell viability, decreased LDH release and MDA formation were observed in cardiomyocytes treated with Allitridum. This cardioprotective effects developed within 12 h, maximized at 24 h and disappeared at 36 h in the optimum concentration (20 μg/ml). The delayed protection was abolished by pretreating with either PKC inhibitor H 7 or PD 98059 (a upstream kinase inhibitor of MAPKs). Conclusion: Allitridum can mimic the delayed cardioprotection in rat neonatal cardiomyocytes. The protective mechanisms is associated with PKC and MAPKs signaling pathways.