目的:研究舒马曲坦诱发大鼠肺动脉平滑肌细胞增殖的作用及其细胞内信号转导通路机制。方法:应用细胞培养、基因转染等方法,通过MTT及流式细胞仪等检测舒马曲坦及ERK1/2的反义寡核苷酸对肺动脉平滑肌细胞增殖及细胞周期的影响。结果:舒马曲坦明显促进肺动脉平滑肌细胞的增殖。脂质体成功介导了寡核苷酸在肺动脉平滑肌细胞的转染。反义寡核苷酸明显抑制舒马曲坦诱导的肺动脉平滑肌细胞增殖,增殖率由(164.67±6.67)%降至(76.67±10.17)%,SPF指数由(11.67±0.33)%降至(3.33±0.33)%,增殖指数由(27.33±0.33)%降至(22.00±0.58)%(P均〈0.01),正义和随机寡核苷酸对舒马曲坦诱导的肺动脉平滑肌细胞增殖则无抑制作用。结论:舒马曲坦通过5-HT1B受体促进大鼠肺动脉平滑肌细胞的有丝分裂,其细胞内信号转导途径为ERK1/2MAPK通路。
Objective: To study the effect of sumatriptan on the proliferation of pulmonary artery smooth muscle ceils (PASMCs)and the mechanism. Methods: The effects of sumatriptan and oligodeoxynucleofides (ODNs) on PASMCs proliferation via extracelluar signalregulated kinase (ERK) were determined by MTI" assay and flow cytometry, respectively. Results: Liposomes mediated the transfecfion of ODNs into PASMCs with high efficiency, Antisense ODN(ASODN)inhibited the proliferation of PASMCs induced by sumatriptan( 1 μmol/L) in vitro, The proliferation rate, S-phase fraction (SPF), and proliferation index (PI)decreased from 164.7%±6,67% to 76.67%±10.17%, from 11,67% ± 0.33% to 3.33% ± 0,33%, and from 27,33%~0.33% to 22.00%±0.58%(P 〈 0.01 ), respectively. Conclusion: The proliferation of PASMCs induced by sumatriptan is dependent on ERK1/2 signal pathway,