【摘要】 目的:探究1-磷酸鞘氨醇(S1P)对缺氧/复氧乳鼠心肌细胞的保护作用及其分子机制。方法:在大鼠乳鼠心肌细胞原代培养基础上,应用液体石蜡覆盖法制备心肌细胞缺氧/复氧模型,采用流式细胞术PI染色法和流式细胞术罗丹明123染色法检测S1P对缺氧/复氧心肌细胞的细胞凋亡和线粒体膜电位的影响;Western Blot分析法检测S1P作用后的心肌细胞p-Akt1蛋白水平变化,并且观察PI3K(磷脂酰肌醇3-激酶)阻断剂渥曼青霉素(wormannin)对S1P上述作用的影响。结果:在S1P的影响下,缺氧/复氧心肌细胞的凋亡率显著下降(P<0.01),线粒体膜电位的去极化被明显抑制(P<0.05),p-Akt1水平明显升高(P<0.01),wormannin能够部分阻断S1P的上述效应。结论:S1P能够显著抑制缺氧/复氧引起的心肌细胞凋亡,其机制可能与S1P激活PI3K-Akt信号通路进而稳定线粒体膜电位有关。更多还原

【Abstract】 Objective:To explore the mechanism of protective effect of Sphingosine-1-phosphate(S1P) in cultured neonatal rat cardiomyocytes during simulated hypoxia/reoxygenation.Methods: On the basis of culturing neonatal rat cardiomyocytes,the model of hypoxia-reoxygennation was built by using method of Liquid Paraffin covering,the impact of S1P on apoptosis and p-Akt and mitochondrial membrane potential were studied by using method of Propidine Iodide staining and Western blot and Rhodamine123 staining.Results: S1P could reduce apoptosis rate(P<0.01) and stabilize the mitochondrial membrane potential(P<0.05) and improved the level of p-Akt1(P<0.01) in hypoxia-reoxygenation cardiomyocytes significantly.But wormannin could block these effects of S1P partially.Conclusion: S1P can obviously restrain apoptosis in curtured rat neonatal cardiomyocytes during simulated hypoxia/reoxygenation.Stabilization of mitochondrial membrane potential by PI3K-Akt signaling pathway is likely to play a role in protective action of S1P.更多还原