新型KATP通道开放剂埃他卡林对人肺动脉平滑肌细胞增殖的影响  

Effects of iptakalim, a novel KATP channel opener, on proliferation of cultured human pulmonary arterial smooth muscle cells induced by endothelin-1

作　　者：倪布清[1] 张石江[1] 朱煜明[2] 张宁[1] 王虹[2] 解卫平[2] 

机构地区：[1]南京医科大学第一附属医院胸心外科,210029 [2]南京医科大学第一附属医院呼吸内科,210029

出　　处：《国际呼吸杂志》2007年第12期903-906,共4页International Journal of Respiration

基　　金：江苏省自然科学基金资助项目（编号：BK2006246）;南京医科大学创新基金（编号：CX2003002）

摘　　要：目的 研究新型KATP通道开放剂埃他卡林（iptakalim）对内皮素-1（ET-1）诱导培养的人肺动脉平滑肌细胞（HPASMC）增殖的影响。方法 内皮素-1诱导培养建立人肺动脉平滑肌细胞增殖模型；氚-胸腺嘧啶核苷（3H—TdR）掺入法观察脱氧核糖核酸（DNA）合成；流式细胞仪技术检测HPASMC细胞周期。结果埃他卡林能剂量依赖性抑制内皮素-1所致的3H—TdR掺入量增多，阻止HPASMC由静止期（G0／G1期）进入DNA合成期（S期）和有丝分裂期（G2／M期）。特异性KATP通道阻断剂格列本脲可拮抗埃他卡林对。H—TdR掺入的抑制作用。结论 埃他卡林可能通过激活KATP通道来抑制ET-1诱导入肺动脉平滑肌细胞的增殖作用，有望成为治疗肺动脉高压的新药。Objective To explore the effects of iptakalim, a novel KATP channel opener, on the proliferation of cultured human pulmonary arterial smooth muscle cells （HPASMC） induced by endothelin-1 （ET-1）, Methods The models of proliferation of HPASMC induced by ET-1 in vitro were established and 3H-thymidine （3H-TdR） incorporation and flow cytometric analysis （FCA） were used. Results The enhanced 3 H-thymidine incorporation was inhibited and the transition of cells from static phase （G0/G1） to DNA synthesis （S） and mitotic phase （G2/M） was held back by iptakalim in a concentration-dependent manner. Glibenclamide abolished the inhibitory effects of iptakalim. Conclusions Iptakalim had the inhibitory effects on the proliferation of HPASMC induced by ET-1 through activation of KATe channels, These findings suggest that iptakalim might be a promising candidate for the treatment of pulmonary arterial hypertension.

关 键 词：埃他卡林 肺动脉平滑肌细胞 内皮素-1 KATP通道 肺动脉高压 

分 类 号：R9[医药卫生—药学]