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目的:观察高密度脂蛋白(HDL)不同组分中1-磷酸鞘氨醇(S1P)的含量对心肌细胞AKT和ERK1/2信号转导通路的影响,探讨HDL对心肌细胞的保护作用。方法:应用超速离心法和层析法,分离不同组分HDL;应用地高辛核素标记法检测各组分中S1P含量。给予小鼠心肌细胞不同S1P含量的HDL组分和S1P1、S1P3受体抑制剂VPC23019刺激后,用蛋白印迹法检测AKT和ERK1/2转导通路磷酸化水平的变化。结果 :与对照组比较,受不同HDL组分刺激后,成年小鼠心肌细胞AKT和ERK1/2磷酸化水平升高,且随着各组分中S1P含量升高,磷酸化水平呈上升趋势,而S1P1及S1P 3受体抑制剂VPC23019能明显阻断此种作用。结论:不同HDL组分通过细胞膜上的S1P受体,激活PI3K-AKT和MEK-ERK1/2信号通路,该作用通过S1P1和S1P3受体介导;HDL可能通过S1P发挥心肌保护作用。
OBJECTIVE: To investigate the effect of sphingosine-1-phosphate monophosphate (S1P) on the AKT and ERK1 / 2 signal transduction pathways in cardiomyocytes and to explore the protective effect of HDL on cardiomyocytes. Methods: The HDL of different components was isolated by ultracentrifugation and chromatography. The content of S1P in each component was detected by digoxin labeling method. The phosphorylation level of AKT and ERK1 / 2 transduction pathway was detected by Western blotting after the HDL component of S1P1 and S1P1, inhibitor of S1P3 receptor were given to mice cardiomyocytes. Results: Compared with the control group, the phosphorylation of AKT and ERK1 / 2 in cardiac myocytes increased after stimulated by different HDL components. With the increase of S1P content in each group, the level of phosphorylation increased, The S1P1 and S1P3 receptor inhibitor VPC23019 can significantly block this effect. CONCLUSIONS: Different HDL components activate the PI3K-AKT and MEK-ERK1 / 2 signaling pathways through the S1P receptor on the cell membrane via S1P1 and S1P3 receptors. HDL may exert myocardial protective effects via S1P.