摘要
目的:观察肾上腺髓质素(ADM)对大鼠心肌成纤维细胞(FBC)胶原合成的影响,并探讨其可能的作用机制。方法:用差速贴壁分离法获得心肌成纤维细胞为材料,用放射免疫法测定细胞培养上清液中I及III型前胶原末端肽(PINP、PCIII)的含量。结果:①ADM呈浓度依赖性抑制FBC的PINP、PCIII分泌;②在AngII存在的情况下,PKA抑制剂能完全阻断ADM抑制细胞PINP、PCIII分泌的作用;③在基础状态和AngII刺激下,PKC及酪氨酸蛋白激酶抑制剂均能增强ADM作用。结论;①ADM能够抑制FBC胶原合成;②ADM抑制FBC胶原合成是通过PKA途径介导。
Objective:To investigate the role of adrenomedullin(ADM) in the synthesis of collagen type I(PINP) and type III(PCIII) in rat cardiac fibroblast,to evaluate its possible intracellular signaling pathway involved.Methods: Neonatal rat cardiac fibroblast(FBC) were isolated and cultured in vitro. The protein content of PINP and PCIII in the cultured medium of treated groups and control groups was determined by radioimmunoassay. Results: ①ADM can inhibit the synthesis of PINP and PCIII both in the basic state and in the state stimulated by AngII in a concentration-dependent manner.②The effect of ADM inhibiting PINP and PCIII secretion can be completely blocked by PKA antagonist.③Both PKC antagonist and tyrosine kinase antagonist can enhance the role of ADM in the basic state and in the state stimulated by AngII. Conclusions:①ADM can inhibit the synthesis of FBC PINP and PCIII.②The PKA pathway is involved in the intracellular signaling of ADM inhibiting FBC collagen synthesis.
