摘要
目的 :研究吡那地尔 (pinacidil,Pin)对内皮素 1(ET 1)诱导培养的兔肺动脉平滑肌细胞 (PASMC)增殖的影响。方法 :内皮素 1刺激培养兔PASMC增殖模型 ;以氚 胸腺嘧啶核苷 ([3 H] TdR)掺入法观察细胞增殖及脱氧核糖核苷酸 (DNA)合成 ;流式细胞仪技术检测兔PASMC细胞周期。结果 :吡那地尔可剂量依赖性的抑制内皮素 1所致的 [3 H] TdR掺入量增多 ,阻止兔PASMC由静止期 (G0 G1期 )进入DNA合成期 (S期 )和有丝分裂期 (G2 M期 )。ATP敏感性钾通道 (KATP)阻断剂格列本脲可拮抗吡那地尔对 [3 H] TdR掺入的抑制作用。结论 :吡那地尔可能通过激活KATP通道抑制内皮素 1诱导兔肺动脉平滑肌细胞的增殖 ,可望用于治疗肺动脉高压时所致的肺动脉重构。
AIM : To explore the effects of pinacidil on the proliferation of rabbit pulmonary arterial smooth muscle cell (PASMC) induced by endothelin 1 in vitro . METHODS : The experimental model of proliferation of rabbit pulmonary arterial smooth muscle cell (PASMC) induced by endothelin 1 in vitro was established and [ 3H] thymidine ([ 3H] TdR) incorporation and flow cytometric analysis (FCA) were used. Z RESULTS : Pinacidil markedly inhibited [ 3H] TdR incorporation of PASMC induced by ET 1 and held back PASMC from static phase (G 0/G 1) to DNA synthesis (S) and mitotic phase (G 2/M) in the dose dependent manner. Glibenclimide blocked the effects of pinacidil on [ 3H] TdR incorporation. CONCLUSION : Pinacidil has an inhibitive effect on PASMC proliferation induced by ET 1 through activating ATP sensitive potassium (K ATP ) channels and K ATP channels might play an important pathophysiologic role in the vascular remodeling. Pinacidil is a promising candidate in the treatment of pulmonary hypertension.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2005年第1期20-23,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家创新药物基础研究重大项目基金 (№ 9690 10 10 1)
国家自然科学基金 (№ 3 9970 846)
江苏省科委社会发展基金 (№BJ2 0 0 0 0 5 1)
江苏省教育厅基金 (№ 0 0KJB3 2 0 0 0 9)
