血管钠肽对中度低氧诱导的心肌细胞蛋白合成有抑制作用

Inhibition of moderate hypoxia-induced protein synthesis by vasonatrin peptide in cultured neonatal rat cardiomyocytes

实验探讨了心房钠尿肽家族新成员血管钠肽 (vasonatrinpeptide ,VNP)对中度低氧诱导的心肌细胞蛋白合成的影响。在培养的新生大鼠心肌细胞上 ,用四唑盐 (MTT)比色实验、总蛋白含量测定和3H 亮氨酸掺入实验等方法观察细胞数和蛋白合成情况 ,并用放免法测定VNP对细胞内环鸟苷酸 (cGMP)和环腺苷酸 (cAMP)以及培养上清液中内皮素含量的影响 ,探讨VNP的作用机制。结果显示 ,重度低氧 2 4h ,心肌细胞数和蛋白合成均降低 ,而中度低氧显著增加蛋白的合成 ,具有促心肌细胞肥大的作用。VNP浓度依赖性地抑制中度低氧诱导的心肌细胞蛋白合成增加 ,并且升高细胞内cGMP水平 ,降低低氧诱导的培养上清液中内皮素的含量。结果提示 :VNP抑制中度低氧诱导的新生大鼠心肌细胞蛋白合成增加 ,该作用与其升高细胞内cGMP浓度、降低低氧诱导的内皮素合成和

The present work was to investigate the effects of vasonatrin peptide (VNP) on cardiomyocyte protein synthesis induced by moderate hypoxia. In cultured neonatal rat cardiomyocytes, MTT methods, total protein measurement and 3H leucine incorporation were used to calculate the cell number and measure the protein synthesis of cardiomyocytes. Furthermore, radioimmunoassay was undertaken to observe the effects of VNP on the intracellular levels of cAMP, cGMP and the concentration of endothelin (ET) in the culture medium. The results showed that both the cell number and protein synthesis decreased with severe hypoxia for 24 h. In contrast, under moderate hypoxia, cardiomyocyte hypertrophy developed; the protein synthesis as evidenced by total protein content and 3H eucine incorporation increased significantly. VNP reduced cardiomyocyte protein synthesis induced by moderate hypoxia in a dose dependent manner. Furthermore, VNP increased the intracellular level of cGMP and decreased the concentration of ET in the culture medium under moderate hypoxia, but had no effect on the level of cAMP. These results suggest that VNP inhibits moderate hypoxia induced protein synthesis in cultured neonatal rat cardiac myocytes. This effect is mediated, at least in part, by an increase in intracellular cGMP, a reduction in synthesis, and/or a release in ET of cardiomyocytes.