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舒马曲坦对大鼠肺动脉平滑肌细胞的促有丝分裂作用

Effect of sumatriptan on pulmonary artery smooth muscle cells proliferation in rats

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【作者】 高山红王怀良李峥陶慧林

【Author】 GAO Shan Hong, WANG Huai Liang, LI Zheng, TAO Hui Lin (Department of Clinical Pharmacology, China Medical University, Shenyang 110001, China)

【机构】 中国医科大学临床药理学教研室解放军202医院药剂科鞍山市中心医院药剂科 辽宁沈阳110001辽宁沈阳110001辽宁鞍山114001

【摘要】 目的 观察 5 HT1B/1D受体激动剂舒马曲坦对肺动脉平滑肌细胞 (PASMC)的促有丝分裂作用 ,探讨其作用机制和诱发肺血管构型重建的可能性。方法 分离培养大鼠PASMC ,用噻唑蓝 (MTT)法检测细胞增殖 ,用流式细胞术法分析细胞周期和DNA合成。结果 MTT法检测 5 羟色胺 (5 HT) 0 .0 1,0 .1,1.0 μmol·L- 1可促进PASMC增殖 ,增殖率分别增加2 0 1% ,2 2 8%和 2 5 6 %。舒马曲坦 0 .0 1,0 .1,1.0μmol·L- 1可促进PASMC增殖 ,增殖率分别增加199% ,2 2 0 %和 2 4 5 %。流式细胞术分析 5 HT 0 .1和1.0 μmol·L- 1组的细胞增殖指数分别为 2 2 .2 %和2 5 .9% ,S期细胞分数分别为 7.2 %和 9.8%。舒马曲坦 0 .1和 1.0 μmol·L- 1组的增殖指数分别为2 1.2 %和 2 3.9% ,S期细胞分数分别为 6 .6 %和8.8% ,均较对照组明显增高 (P <0 .0 5 )。 5 HT和舒马曲坦能够促进PASMC从G0 /G1期进入S期 ,5 HT的促有丝分裂作用可能有 5 HT1B/1D受体的参与。结论 舒马曲坦能促进PASMC的增殖。 5 HT1B/1D 受体在PASMC增殖和肺血管构型重建中有重要作用。舒马曲坦有致肺动脉高压的风险

【Abstract】 AIM To study the effects of sumatriptan, a 5 HT 1B/1D receptor agonist, on proliferation of pulmonary artery smooth muscle cells (PASMC), to investigate the involvement of 5 HT 1B/1D receptor in pulmonary remodeling. METHODS Cultured PASMC were isolated from rat pulmonary artery. The proliferation of PASMC was evaluated by MTT assay and flow cytometry. RESULTS By MTT assay, 5 hydroxytryptamine (5 HT) 0.01, 0.1, 1.0 μmol·L -1 stimulated increase in PASMC by 201%, 228% and 256%, respectively. Sumatriptan 0.01, 0.1 , 1.0 μmol·L -1 stimulated increase in PASMC by 199%, 220% and 245%, respectively. The proliferation index (PI) of PASMC stimulated by 5 HT 0.1 and 1.0 μmol·L -1 was 22.2%, 25.9% and S phase cell fraction (SPF) was 7.2%, 9.8%, respectively. PI of PASMC stimulated by sumatriptan 0.1 and 1.0 μmol·L -1 was 21.2%, 23.9%, SPF was 6.6%, 8.8%, respectively. Sumatriptan promoted PASMC from the G 0/G 1 into S phase, indicating that 5 HT 1B/1D receptors may involved in the proliferation of PASMC induced by 5 HT and sumatriptan. CONCLUSION Sumatriptan promotes PASMC growth. 5 HT 1B/1D receptors may be important in PASMC proliferation and pulmonary remodeling.

【基金】 国家自然科学基金资助项目 ( 30 2 715 10 )~~
  • 【文献出处】 中国药理学与毒理学杂志 ,Chinese Journal of Pharmacology and Toxicology , 编辑部邮箱 ,2003年04期
  • 【分类号】R965
  • 【被引频次】8
  • 【下载频次】56
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