摘要
目的:研究普罗布考抑制碱性成纤维细胞生长因子(bFGF)和H2O2促大鼠主动脉平滑肌细胞(RASMCs)增殖的机制。方法:采用MTT、[3H]-TdR掺入法、流式细胞术和RT-PCR观察普罗布考对bFGF和H2O2刺激条件下细胞周期、细胞增殖和凋亡的影响。结果:①普罗布考抑制bFGF和H2O2刺激RASMCs增殖。细胞计数、A值和[3H]-TdR掺入量分别下降了40.0%、39.1%、45.5%和46.9%、45.0%、39.5%(P<0.05,P<0.01)。②普罗布考使RASMCs生长停滞在G0/G1期,抑制bFGF刺激的细胞增殖,通过诱导细胞凋亡和抑制细胞生长2种方式抑制H2O2刺激的细胞增殖。③bFGF和H2O2分别使ERK1mRNA表达量增加近4倍和6倍,MKP-1mRNA表达量下降了62.4%和82.2%。普罗布考抑制ERK1mRNA表达,使H2O2诱导的MKP-1表达下降上调,而对bFGF诱导MKP-1表达下降无明显影响。结论:普罗布考通过降低ERK1mRNA表达抑制细胞周期运转和诱导RASMCs凋亡,从而抑制bFGF和H2O2刺激引起的细胞增殖。
AIM： To investigate the antiproliferative mechanisms of probucol in rat aortic smooth muscle cells （RASMCs） stimulated by basic fibroblast growth factor （bFGF） and hydrogen peroxide （H2O2 ）. METHODS： Effects of probucol on cell cycle, DNA synthesis, proliferation and apoptosis in the presence of bFGF and H2O2 were Observed by means of MTT test, cell number counting, [^3H] -TdR incorporation, FCM and RT-PCR. RESULTS： ①Probucol sig-nificantly inhibited proliferation and DNA synthesis in RASMCs stimulated by bFGF and H2O2 , with a dose - dependent manner. Cell numbers, A value and [^3H] -TdR incorporation in probucol ＋ bFGF group and probucol ＋ H2O2 group were reduced by 40. 0%, 39. 1%, 45.5% and 46. 9%, 45. 0%, 39. 5%, respectively, compared with bFGF group and H202 group （P 〈0.05, P 〈0.01, respectively）. ②Probucol protected against bFGF - induced VSMCs proliferation through inducing cell growth arrested at G0/G1 phase and H2O2 - induced RASMCs proliferation through inducing cell apoptosis as well as cell growth arrested at G0/G1 phase. ③bFGF and H2O2 increased ERK1 mRNA expression by 4 and 6 times and decreased MKP - 1 mRNA expression to 62. 4% and 82. 2%, respectively, compared with controls. Probucol attenuated the increases in bFGF- and H2O2 -stimulated ERK1 mRNA level and up- regulated H2O2 -decreased MKP- 1 mRNA level, however, no effect on MKP- 1 mRNA expression down-regulated by bFGF was observed. CONCLUSION： Probucol, dramatically suppresses bFGF -and H2O2-stimulated RASMCs proliferation by inhibiting cell cycle progression via down -regulating ERK1 mRNA transcriptional level, as well as inducing cell apoptosis.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2008年第5期856-861,共6页
Chinese Journal of Pathophysiology
基金
山东省自然科学基金重点资助项目(No.Z2006C07)
