中国药理学与毒理学杂志2011，Vol.25Issue(1)：17-22,6.DOI:10.3867/j.issn.1000-3002.2011.01.004
选择性内皮素A型受体拮抗剂GF063对内皮素-1诱导的心肌细胞肥大的影响
Effect of GF063, a new selective antagonist of endothelin A receptor,on cardiomyocytes hypertrophy induced by endothelin-1
摘要
Abstract
OBJECTIVE To investigate the effect of new endothelin A receptor ( ETA ) antagonist,di-n-butylaminocarbamyl-L-leucyl-D-tryptophanyl-D-4-chloro-Phe ( GF063 ), on cardiomyocytes hypertrophy induced by endothelin-1 (ET-1).METHODS A primary culture of neonatal SD rat cardiomyocytes was prepared by differential adhesion.Cytotoxicity was determined by MTT assay,cell surface area was calculated by optical microscopy with image processing software, protein synthesis was measured by incorporation of [3H]leucine, and gene expression was assessed by RTPCR.RESULTS Compared with normal control group, after treatment with ET-1 10 nmol·L-1 for 24 h, the surface area, incorporation of [3H]leucine and ANP mRNA expression in cardiomyocytes cells increased by 80.6％, 73％ and 80％ (P ＜ 0.05 ), respectively.Cardiomyocytes treated with GF063 1 nmol· L- 1 - 10 μmol· L - 1 alone for 24 h produced neither obvious cytotoxicity nor hypertrophy.GF063 1 μmol·L-1 +ET-1 10 nmol·L-1 in cardiomyocytes for 24 h could inhibit the increase of cardiomyocytes surface area induced by ET-1, and the inhibition rate was 31.3％ (P ＜0.05 ).GF063 1 and 10 μmol·L-1 +ET-1 10 nmol· L-1 in cardiomyocytes for 24 h could inhibit increases in incorporation of [3H]leucine induced by ET-1, and the inhibition rate was nearly 100％ (P ＜0.05 ).GF063 10 μmol·L-1 + ET-1 10 nmol· L-1 in cardiomyocytes for 24 h could inhibit increases of ANP mRNA expression induced by ET-1 at a rate of 82.6％ ( P ＜ 0.05).GF063 produced a similar effect to positive control drug BQ123 on cardiomyocytes hypertrophy induced by ET-1.CONCLUSION GF063, as a selective ETA receptor antagonist, can inhibit the hypertrophy of cardiomyocytes induced by ET-1.关键词
GF063/受体,内皮素A/肌细胞,心脏/心肌肥厚分类
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张翠,孔令雷,颜玲娣,梁远军,刘克良,宫泽辉..选择性内皮素A型受体拮抗剂GF063对内皮素-1诱导的心肌细胞肥大的影响[J].中国药理学与毒理学杂志,2011,25(1):17-22,6.基金项目
国家高技术研究发展计划(863计划)重大专项基金资助项目(2006AA020601) （863计划）
国家"重大新药创制"科技重大专项资助项目(2009ZX09503-015) （2009ZX09503-015）
