17β-雌二醇抑制碱性成纤维细胞生长因子诱导的血管外膜成纤维细胞增殖

17β-estradiol inhibits basic fibroblast growth factor-induced vascular adventitial fibroblast proliferation

目的探讨17β-雌二醇（E2）对碱性成纤维细胞生长因子（bFGF）诱导的血管外膜成纤雏细胞（VAF）增殖的影响。方法将培养的血管外膜成纤维细胞分4组：对照组，单纯bFGF组，单纯E2组，bFGF4＋E2组。用3^H-Tdr掺入反映细胞DNA合成、3^H-Proline掺入反映细胞的胶原合成状况；用Western Breeze检测血管外膜成纤维细胞中细胞外信号调节蛋白激酶（ERK）、丝裂原活化蛋白激酶磷酸酶-1（MKP-1）的蛋白表达及活性。结果bFGF使血管外膜成纤维细胞DNA合成增加18-23倍、胶原合成增加17-21倍、细胞数目增加18—22倍，E2可使bFGF的这些促血管外膜成纤维细胞增殖效应降低约50％。bFGF使VAF中ERK蛋白表达量增加350％，使ERK磷酸化蛋白表达量增加120％，B使bFGF诱导的VAF中ERK蛋白表达量下降44％，ERK磷酸化蛋白表达量下降22％；E2使bFGF诱导的VAF中MKP-1的蛋白表达量增加154％。结论E2可抑制bFGF诱导的VAF增殖，其抑制VAF增殖与抑制、VAF中ERK蛋白表达，降低ERK活性，促进MKP-1表达有关。

Objective To assess the effects of 17β-estradiol （E2） on basic fibroblast growth factor （bFGF）-induced vascular adventitial fibroblast （VAF） proliferation and the role of mitogen activated protein kinase （MAPK） signaling pathway in it. Methods Cultured VAFs were divided into four groups： control group, E2 group, bFGF group, E2 ＋ bFGF group. 3^ H-thymidine incorporation study was done to investigate DNA synthesis and 3^H-proline incorporation study was done to investigate collagen synthesis. The protein expression and activity of ERK and mitogen-activated protein kinase phosphatase-1 （MKP-1 ） were examined by Western breeze. Resuits VAF was stimulated by 2 pg/L bFGF, resulting in that its DNA synthesis increased by 18 - 23 folds, collagen synthesis increased by 17 - 21 folds and the cell number increased by 18 - 22 folds. 10^8 mol/L 17β- estradiol decreased these effects of bFGF by 50% .2 pg/L bFGF caused that ERK protein expression increased by 350% and ERK phosphorylated protein expression increased by 120%; while 10-8 mol/L 17β-estradiol caused that ERK protein expression decreased by 44%, ERK phosphorylated protein expression decreased by 22% and MKP-1 protein expression increased by 154%. Conclusion 17β-estradiol can inhibit bFGF-induced VAF proliferation, inhibit protein expression and activity of ERK and induce protein expression of MKP-1.