摘要
目的:研究一氧化氮(NO) 及一氧化碳(CO) 对碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF) 促平滑肌细胞(vascularsmooth muscle cells, VSMC)增殖作用的影响及其机制。方法:以3HTdR参入法测定平滑肌细胞增殖程度,放射活性法测定VSMC内蛋白磷酸化程度、蛋白激酶C(protein kinase C,PKC) 及丝裂素活化蛋白激酶(mitogenactivated protein kinase, MAPK)活性。结果:孵育24 h 后,bFGF刺激的VSMC增殖较对照组增加1.1 倍(P< 0.01),细胞内蛋白磷酸化程度增加38.2% (P< 0.01),PKC 及MAPK 活性分别增加1.5 和2 .5倍( P< 0.01);CO 前体hemeLlysinate(HLLys) 及NO 前体LArginine( LArg) 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;5、10 、20 μmol·L-1 HLLys 使bFGF刺激的VSMC增殖分别减少43.4 % 、46.6% 和47 .6%
Objective: To investigate the effect of nitric oxide(NO) and carbon monoxide(CO) on proliferation of vascular smooth muscle cells(VSMC) stimulated by basic fibroblast growth factor(bFGF) and their mechanism. Methods: VSMC proliferation was measured by 3H TdR incorporation. Protein phosphorylation, PKC and MAPK activity in VSMC were determined by radioactivity assay. Results: Compared with control, VSMC amplification induced by bFGF was increased by 1.1 fold after 24 h incubation ( P <0.01). Protein phophorylation, PKC and MAPK activities in VSMC were augmented by 38.2%, 1.5 and 2.5 times, respectively ( P <0.01); H L Lys and L Arg had no significant influence on both growth and intracellular protein phosphorylation, PKC and MAPK activities in quiescent VSMC. 5, 10 and 20 μmol·L -1 H L Lys decreased bFGF stimulated VSMC proliferation by 43.4%,46.6% and47.6%,respectively ( P <0.01). Intracellular PKC activities were lowered by 25.6%, 31.8% and 33.9%, respectively ( P <0.01), and MAPK activities were reduced by 15.0%, 25.5% and 40.1%, respectively ( P <0.01); 5, 10 and 20 mmol·L -1 L Arg decreased bFGF stimulated VSMC proliferation by 30.2%, 40.5% and 51.9%, respectively ( P <0.01). Intracellular PKC activities were lowered by 29.8%, 28.9% and 36.6%,respectively ( P <0.01), and MAPK activities were reduced by 19.4%, 32.4% and 44.4%, respectively ( P <0.01). bFGF induced protein phosphorylation in VSMC was inhibited by 10 μmol·L -1 H L Lys and 10 mmol·L -1 L Arg by 31.8% and 37.4%, respectively ( P <0.01). Conclusion: NO and CO may have an inhibitive role against VSMC proliferation caused by bFGF, whose mechanism has a close relationship with inhibition of intracellular protein phosphorylation, PKC and MAPK activities stimulated by bFGF.
出处
《北京医科大学学报》
CSCD
1999年第6期524-527,共4页
Journal of Peking University(Health Sciences)
基金
国家自然科学基金
"九五"国家科技攻关项目
关键词
一氧化氮
一氧化碳
药理学
BFGF
血管平滑肌
Nitric oxide/pharmacol
Carbon monoxide/pharmacol
Fibroblast growth factor
basic/pharmacol
Muscle
smooth
vascular/drug eff