内皮缩血管肽A受体拮抗剂ETP-508对内皮缩血管肽1诱导的心肌细胞肥厚的作用

Effects of an endothelin A-receptor antagonist ETP-508 on endothelin-1-induced cardiomyocyte hypertrophy

目的观察内皮缩血管肽(ET)A受体拮抗剂ETP-508对ET-1诱导的心肌细胞肥厚的作用。方法心肌细胞用ET-1(10nmol·L-1)或ET-1+ETP-508(10μmol·L-1)处理24h,分别采用光学显微镜、[3H]亮氨酸掺入、激光扫描共聚焦显微镜和RT-PCR技术方法观察ETP-508对心肌细胞表面积、蛋白质合成、肌原纤维肌节重新组装和基因表达的影响。结果ET-110nmol·L-1诱导心肌细胞表面积和[3H]亮氨酸掺入增加,胚胎基因心钠素和肌球蛋白轻链2的mRNA表达增加,肌原纤维节重新形成;ETP-50810μmol·L-1可显著抑制ET-1诱导的心肌细胞表面积和[3H]亮氨酸掺入增加,抑制率分别达56%和46%;并显著减弱肌原纤维节的重新形成和胚胎基因的再表达。结论ETP-508对ET-1诱导的乳大鼠心肌细胞肥厚有显著的阻断作用。

AIM To observe the effects of endothelin A-receptor antagonist ETP-508 on cardiomyocyte hypertrophy-induced by endothe- lin-1 （ET-1） in neonatal rat cardiomyocytes. METHODS Cardiomyocytes were exposed to ET-1 （ 10nmol·L^-1 ） or ET-1 combined with ETP-508 （ 10 μmol·L^-1） treatment for 24 h. Cardiomyocytes surface area, incorporation of [ 3H ] leucine, sarcomere reorganization and gene expression were evaluated by optical microscopy, [ 3H ] leucine incorporation, laser scanning confocal microscopy and RT-PCR, respectively. RESULTS Increases in myo- eyte surface area and incorporation of [ 3H ] leucine, mRNA expression of embryo genes atrial natriuretic factor and myoglobin light chain-2, and sarcomere reorganization were observed in the model of cardiomyocytes hypertrophy induced by ET-1 10nmol·L^-1. ETP-508 10μmol·L^-1 significantly inhibited ET-1 induced increases in myocyte surface area and [ 3H ] leucine uptake, and the inhibition rate was 56% and 46%, respectively. Furthermore, ETP-508 significantly attenuated sarcomere reorgani- zation and embryo gene re-expression. CONCLUSION ETP-508 remarkably abolishes ET-l-induced rat neonatal cardiomyocytes hypertrophy.