几种扩血管多肽对bFGF促血管平滑肌细胞增殖作用的影响

EFFECT OF ADRENOMEDULLIN、CALCITONIN GENE-RELATED PEPTIDE AND C-TYPE NATRIURETIC PEPTIDE ON BFGF-STIMULATED PROLIFERATION OF VASCULAR SMOOTH MUSCLE CELLS

目的和方法 :研究肾上腺髓质素 (Adm)、降钙素基因相关肽 (CGRP)及C 型心房利钠肽 (CNP)对碱性成纤维细胞生长因子 (bFGF)促血管平滑肌细胞 (VSMC)增殖作用的影响及其机制。结果 :孵育 2 4h后 ,bFGF刺激VSMC增殖较对照组增加 2 1倍 (P <0 0 1) ,细胞内蛋白磷酸化程度增加 1 4倍 (P <0 0 1) ,PKC及MAPK活性分别增加 1 5和 2 5倍 (P <0 0 1) ;Adm .CGRP和CNP对静止期VSMC生长无显著影响 ,亦未引起细胞内蛋白磷酸化、PKC及MAPK活性发生显著改变 (P >0 0 5 ) ,10 -8、10 -9和 10 -10 mmol/L、Adm、CGRP和CNP均呈浓度依赖性抑制bFGF刺激的VSMC增殖 (均P <0 0 1) ,降低VSMC内PKC和MAPK活性 (均P <0 0 1) ,减轻bFGF促进的VSMC内蛋白磷酸化程度 (均P <0 0 1)。结论 :Adm、CGRP和CNP可抑制bFGF刺激的大鼠VSMC增殖 。

Aim and methods:To investigate the effect of adrenomedullin(Adm),calcitonin generelated peptide(CGRP)AND Ctype natriuretic peptide(CNP) on proliferation of vascular smooth muscle cells(VSMC)stimulated by basic fibroblast growth factor(bFGF) and their mechanism.Results:VSMC amplification induced by bFGF increased by 2.1fold after 24h incubation (P<0.01),protein phosphorylation,PKC and MAPK activity in VSMC augmented by 1.4,1.5 and 2.5 times,respectively(P<0.01).Adm,CGRP and CNP had no significant influence on both growth and intracellular protein phosphorylation,PKC and MAPK activities in quiescent VSMC. 10 -8 ,10 -9 and 10 -10 mol/L Adm,CGRP and CNP decreased bFGFstimulated VSMC proliferation(P<0.01),lowered PKC and MAPK activitities in VSMC(P<0.01), and decreased protein phosphorylation in VSMC stimulated by bFGF(P<0.01) in a dosedependent way.Conclusion:Adm,CGRP and CNP may have an antagonistic role against VSMC proliferation caused by bFGF, which mechanism has a close relationship with inhibition of intracellular protein phosphorylation, PKC and MAPK activities stimulated by bFGF.