摘要
目的观察内皮素-1(ET-1)及其受体(ETR)对心肌细胞肥大和心脏成纤维细胞增殖的作用。方法体外乳鼠心肌细胞和心脏成纤维细胞培养,一定浓度的ET-1作用细胞24h,以3H-胸腺嘧啶核苷(3H-TdR)、3H-亮氨酸(3H-Leu)掺入法测定细胞DNA、蛋白质合成,Bradford法测定细胞总蛋白含量,RT-PCR法测定心肌细胞心钠素(ANP)mRNA的表达;用针对ETA受体(ETAR)、ETB受体(ETBR)的特异性拮抗剂BQ123、BQ788分别阻断两个受体,观察两种受体的作用。结果ET-1显著促进心肌细胞和心脏成纤维细胞3H-TdR、3H-Leu掺入,总蛋白含量增加,ET-1的作用呈剂量依赖性,并且使心肌细胞ANP mRNA表达明显增加,ET-1的作用可被ETAR拮抗剂BQ123明显抑制,ETBR拮抗剂BQ788对此无影响。结论ET-1促进心肌细胞肥大和心脏成纤维细胞增殖,ET-1的作用通过ETAR介导,ETBR对此无明显作用。
Objective To investigate the role of endothelin-1 and its receptors on hypertrophy or proliferation of cultured cardial cells. Methods Cardiomyocytes and cardiac fibroblasts were isolated by trypsin digestion method, DNA and protein synthesis were measured by ^3 H-dexyribonucleotidethymine （^3 H-TdR） and ^3H-Leucine （ ^3 H-Leu） incorporation, while protein content was measured by Bradford method. Atrial natriuretic peptide （ ANP ） mRNA expression of cardiomyocyte was measured by reverse transcripted-polymerase chain reaction. Selective endothelin （ET） receptor subtype antagonists BQ123 and BQ788 were used to block ETA receptors （ETAR） and ETBR respectively and to observe the effects of the two receptors during cardiac hypertrophy. Results ET-1 significantly increased the^3 H-TdR and ^3H-Leu incorporation rate of cardiomyocytes and cardiac fibroblasts in a close-dependent manner and increased protein content. Furthermore, ET-1 promoted the ANP mRNA expression of cardiomyocyte. ETA R antagonist remarkably blocked these effects, while ETBR antagonist had no obvious effect. Conclusions ET-1 can induce the hypertrophy for cardiomyocytes and the proliferation for cardiac fibroblasts. These effects are mediated by ETAR.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2006年第4期520-523,共4页
Acta Academiae Medicinae Sinicae
基金
国家重点基础研究发展规划(973)(G2000056905)~~
