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四氢吡喃类药物对血小板激活因子诱导的脑微血管平滑肌细胞DNA合成及增殖的拮抗作用
摘    要:研究了血小板激活因子(PAF)对兔血小板聚集,牛脑微血管平滑肌细胞DNA合成及增殖的影响及四氢吡喃类药物trans-2,6-bis-(3,4-dimethoxy-phenyl)-tetrahydro-(4H)pyran(SZ-1)和trans-2-(3,4,5-trimethoxyphenyl)-6-(2,4-difluo-rophenyl)-tetrahydro-(4H)pyran(DFTM)的拮抗作用.结果表明:PAF强烈刺激兔血小板聚集,在1.91μmol·L-1时,刺激的百分率为71.7%.SZ-1和DFTM剂量依赖性地抑制PAF刺激的兔血小板聚集,IC50分别为0.39和0.84nmol·L-1.PAF还刺激牛脑微血管平滑肌细胞增殖,在0.1nmol·L-1时作用48h达最大效应.SZ-1和DFTM显著抑制血小板激活因子的上述作用,在1nmol·L-1时抑制率分别为25.9%和30.7%.SZ-1和DFTM还抑制PAF刺激的牛脑微血管平滑肌细胞DNA合成,在1nmol·L-1时抑制率分别为29.1%和24.4%.实验结果表明:PAF可能通过促进血小板聚集,刺激脑血管平滑肌细胞增殖及DNA合成而参与?

关 键 词:血小板激活因子;细胞,培养的;细胞增殖;血小板聚集;四氢吡喃衍生物

Antagonistic effects of tetrahydropyrans on platelet activating factor-induced DNA synthesis and proliferation of cerebromicrovascular smooth muscle cells 1
Abstract:The antagonistic effects of trans-2,6- bis-(3,4-dimethoxyphenyl)-tetrahydro-(4H) pyran (SZ-1) and trans-2-(3,4,5-trimethoxyphenyl)-6-(2,4-difluoro- phenyl)-tetrahydro-(4H)pyran (DFTM) on rabbit platelet aggregation, DNA synthesis and proliferation of bovine cerebromicrovascular smooth muscle cells (BCSMC) induced by platelet activating factor (PAF) were investigated. The results showed that PAF strongly stimulated rabbit platelet aggregation and at 1.91 μmol·L -1 the stimulatory rate is 71.7%. Both drugs inhibited PAF-induced rabbit platelets aggregation in a dose-dependent manner and their IC 50s were 0.39 and 0.84 nmol·L -1 , respectively for SZ-1 and DFTM. Also, PAF significantly stimulated the proliferation of BCSMC and reached maximal effect at 48 h at 0.1 nmol·L -1 . SZ-1 and DFTM at 1 nmol·L -1 inhibited PAF-induced proliferation of BCSMC by 25.9% and 30.7%, respectively. PAF meanwhile promoted the DNA synthesis of BCSMC and SZ-1, DFTM, at 1 nmol·L -1 inhibited PAF-induced DNA synthesis by 29.1% and 24.4%, respectively. The results indicate that PAF stimulating platelet aggregation and the proliferation of BCSMC might be one of the events which PAF contributes to the pathogenesis of cerebral atherosclerosis. SZ-1 and DFTM might have a potential application in the prevention and treatment of cerebrovascular disorders.
Keywords:platelet activating factor  cells   cultured  cell proliferation  platelet aggregation  tetrahydropyran derivatives
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