Salusins对大鼠离体心脏及心肌细胞的生物学效应的研究

Bio-effects of salusins on isolated rat heart and neonatal cardiomyocytes

目的 :研究新发现的心血管活性肽salusin的心脏及心肌细胞的生物学效应。方法 :利用Langendorff装置灌流的成年大鼠离体心脏及原代培养的乳鼠心肌细胞 ,测定心功能和心肌细胞 [45Ca2 + ]摄入及 [3 H]-亮氨酸([3 H]-Leu)掺入量。结果 :10 -12 - 10 -7mol/Lsalusin -α及salusin - β对成年大鼠离体心脏功能无明显影响 ;但10 -10 - 10 -6mol/Lsalusin -α及salusin - β均呈浓度依赖性地促进心肌细胞 [45Ca2 + ]摄入及 [3 H]-Leu掺入 ,其效应在 10 -8mol/L时达峰值 ;salusin -α及salusin - β对心肌细胞 [45Ca2 + ]摄入的效应可被钙通道阻断剂尼卡地平(nicardipine)所拮抗 ,且与内皮素有协同效应。Salusin -α及salusin - β对心肌细胞 [3 H]-Leu掺入的效应可被尼卡地平、钙调磷酸酶抑制剂FK5 0 6、丝裂原活化蛋白激酶 (MAPK)阻断剂PD980 59及蛋白激酶C(PKC)阻断剂chelerthinechloride等不同程度抑制。Salusin - β对心肌细胞 [45Ca2 + ]摄入的效应强于salusin -α,但 [3 H]-Leu掺入的效应两者之间无显著性差异。结论 :Salusin -α及salusin - β对成年大鼠离体心脏功能无直接效应 ,但能促进乳鼠心肌细胞钙摄入及蛋白合成 ,其效应可能与钙通道、钙调神经磷酸酶、MAPK和PKC等信号转导途径有关。Salusin可?

AIM: To investigate the bio-effects of salusins on rat heart and cardiomyocytes. METHODS: The cardiac function was determined by multipurpose polygraph in isolated rat heart treated with various concentrations of salusin-α or salusin-β. [ 45Ca 2+] and [3H]-Leu incorporation were determined in cultured neonatal rat cardiomyocytes with β-liquid scintillation counter. RESULTS: 10 -12-10 -7mol/L salusin-α and salusin-β had no effects on isolated rat cardiac function. However, salusin-α and salusin-β stimulated [ 45Ca 2+] uptake and [3H]-Leu incorporation. The [ 45Ca 2+] uptake induced by salusins were inhibited by nicardipine, and were synergistically increased by endothelin-1. The [3H]-Leu incorporation induced by salusin-α and salusin-β was inhibited by nicardipine, FK506 (a special inhibitor of carcineulin), PD 98059 (inhibitor of MAPK) and chelerthine (inhibitor of PKC). The effects of salusin-β on [ 45Ca 2+] uptake was stronger than those of salusin-α. But there were no statistical difference in [3H]-Leu incorporation between salusin-α and salusin-β. CONCLUSIONS: Salusin-α and salusin-β did not affect directly cardiac function in rat hearts. But salusins improved calcium uptake and protein synthesize in neonatal rat cardiomyocytes. Those effects of salusins were related with calcium channel, carcinuelin, MAPK and PKC signal pathways. Salusins may be the regulatory factors for myocardium growth and hypertrophy.