新型ATP敏感性钾通道开放剂埃他卡林对兔肺动脉平滑肌细胞增殖的影响  

Effects of iptakalim on the proliferation of cultured rabbit pulmonary arterial smooth muscle cells induced by endothelin-1

作　　者：解卫平[1] 王虹[1] 齐栩[1] 沈红[1] 汪海 胡刚[3] 

机构地区：[1]南京医科大学第一附属医院呼吸内科,210029 [2]北京军事医学科学研究院药理毒理所 [3]南京医科大学药理系

出　　处：《中华结核和呼吸杂志》2004年第11期752-755,共4页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：国家创新药物基础研究重大项目基金资助项目 ( 9690 10 10 1);国家自然科学基金资助项目( 3 9970 846);江苏省科委社会发展基金资助项目 (BJ2 0 0 0 0 5 1);江苏省教育厅基金资助项目 ( 0 0KJB3 2 0 0 0 9)

摘　　要：目的　观察埃他卡林 (IPT)对内皮素 1(ET 1)诱导培养的兔肺动脉平滑肌细胞 (PASMC)增殖的作用 ,并探讨其作用机制。方法　ET 1诱导培养的兔PASMC增殖 ,氚 胸腺嘧啶核苷 ([3 H] TdR)掺入法检测DNA合成 ;流式细胞仪技术检测细胞周期。结果　ET 1(10 -7mol/L)使PASMC [3 H] TdR掺入量增加 14 6 8% ,与对照组比较差异有显著性 (P <0 0 1) ;在相同条件下 ,加入ET 1的同时 ,分别向培养基中加入IPT 10 -7、10 -6、10 -5mol/L ,细胞 [3 H] TdR掺入量分别下降 (19 8± 4 6 ) %、(4 1 2±9 5 ) %、(5 4 7± 10 1) % ,与ET 1组比较差异有显著性 (P <0 0 1) ;培养基中加入ET 1(10 -7mol/L)、IPT(10 -5mol/L)前 30min ,预先加入格列本脲 10 -7、10 -6、10 -5mol/L ,其 [3 H] TdR掺入量分别增加(4 9 1± 8 7) %、(6 8 6± 15 1) %、(110 1± 2 6 8) %。流式细胞仪细胞周期检测显示ET 1(10 -7mol/L)刺激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 ) ,其G0 /G1期比例降低 (2 2 0 4± 1 0 7) % ,与对照组比较差异有显著性 (P <0 0 1) ,而S期与G2 /M期之和增加 (2 10 1±37 9) % ,与对照组比较差异有显著性 (P <0 0 1) ;相同条件下 ,加入ET 1(10 -7mol/L)的同时 ,分别加入IPTObjective To explore the effects of iptakalim on the proliferation of rabbit pulmonary arterial smooth muscle cell(PASMC) induced by endothelin-1(ET-1) in vitro. Methods The experimental models of proliferation of rabbit PASMC induced by ET-1 in vitro were established and [ 3H]-thymidine([ 3H]-TdR)incorporation and flow cytometric analysis(FCA) were used. Results The value of [ 3H]-TdR incorporation in ET-1 group was increased 1.468 times higher than that in control guoup. Iptakalim at the concentrations of 10 -7 mol/L,10 -6 mol/L,10 -5 mol/L lowered [ 3H]-TdR incorporation by (19.8±4.6)%,(41.2±9.5)%,(54.7±10.1)%,declined the total of the DNA synthesis(S) and the mitotic phase (G 2/M) ratios by (36.6±5.7)%,(42.6±4.9)%,(66.3±4.7)%,and increased the static phase(G 0/G 1) ratio by (14.4±3.0)%,(17.9±2.6)%,(27.9±3.2)%,respectively,compared with the value of the cells treated with ET-1 only(P<0.01). Glibenclimide abolished the effect of iptakalim on [ 3H]-TdR incorporation. Conclusion Iptakalim has an inhibitory effect on PASMC proliferation induced by ET-1 through activating ATP sensitive potassium(K ATP) channels.

关 键 词：ET-1 增殖 埃他卡林 对照组 肺动脉平滑肌细胞 ATP敏感性钾通道开放剂 DNA合成 显著性 目的观 差异 

分 类 号：R96[医药卫生—药理学]