埃他卡林对兔肺动脉平滑肌内皮细胞钙浓度的影响  

Effects of iptakalim on intracellular free calcium concentration of cultured rabbit pulmonary arterial smooth muscle cells

作　　者：齐栩[1] 王虹[1] 解卫平[1] 胡刚[2] 汪海[3] 

机构地区：[1]南京医科大学第一附属医院呼吸内科,江苏南京210029 [2]南京医科大学基础医学院药理系,江苏南京210029 [3]北京军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药理学通报》2008年第1期67-70,共4页Chinese Pharmacological Bulletin

基　　金：国家创新药物基础研究重大项目基金资助(No969010101);国家自然科学基金资助项目(No39970846);江苏省科委社会发展基金资助项目(NoBJ2000051);江苏省教育厅基金资助项目(No00KJB320009)

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)增殖的影响,并探讨其作用机制。方法应用细胞培养、氚-胸腺嘧啶核苷([3H]-TdR)参入实验、Fluo-3和激光扫描共聚焦显微镜技术评价IPT对ET-1诱导的兔PASMC增殖及PASMC[Ca2+]i调节的作用。结果ET-1(10-7mol.L-1)使PASMC[3H]-TdR参入量增加146.8%,与对照组比较,差异有显著性(P<0.01);在相同条件下,加入ET-1的同时,分别向培养基中加入IPT10-7、10-6、10-5mol.L-1,细胞[3H]-TdR参入量分别下降(19.8±4.6)%、(41.2±9.5)%、(54.7±10.1)%,与ET-1组比较差异有显著性(P<0.01);对照组PASMC[Ca2+]i荧光强度和荧光光密度值较低;ET-1组中[Ca2+]i荧光光密度值明显增高,从73.7±10.1增加到143.8±28.2,两者比较差异有显著性(P<0.01);而IPT组细胞内荧光光密度值明显降低,仅从74.30±10.2增加到86.03±9.82,与ET-1组比较差异有显著性(P<0.01)。结论IPT可明显抑制ET-1诱导的兔PASMC增殖、DNA合成;减少钙通道的开放时间,抑制细胞内Ca2+浓度增加。Aim To explore the effects of iptakalim on intracellular free calcium concentration of cultured rabbit pulmonary arterial smooth muscle ceils induced by endothelin-1 （ ET-1 ） in vitro. Methods A cell culture model and [^3H ] -thymidine （ [^3H ] -TdR） incorporation and confocal microscope were used to observe proliferation and[ Ca^2＋] i of rabbit PASMC induced by ET-1 in vitro. Results The value of [^H ]-TdR incorporation in ET-1 group increased 1. 468 times higher than that in control group. Ipt at the concentration of 10^-7, 10^-6,10^-5 mol· L^-1 lowered [^3H ] -TdR incorporation by（19.8 ±4.6）%,（41.2 ±9.5）%,（54.7 ± 10. 1 ） %, respectively, compared with the value of the cells treated with ET-1 （ P 〈 0. 01 ） ; the intracellular fluorescence intensity of PASMC in ET-1 group increased from 73.70 ± 10. 12 to 143.84 ±28.23 ,significantly higher than that in control group （ P 〈 0. 01 ） ; whereas with Ipt, the fluorescence intensity （FI） only increased from 74. 30 ± 10. 2 to 86. 03± 9.82, significantly lower than that in ET-1 group（P 〈0. 01 ）. Conclusions Iptakalim inhibits proliferation of PASMC and decreases intracellular free calcium concentration of cultured rabbit PASMC indced by ET-1.

关 键 词：肺动脉高压 ATP敏感性钾通道 钙通道 内皮细胞 

分 类 号：R-332[医药卫生] R322.74