SB_(224289)对5-HT诱导的肺动脉平滑肌细胞增殖的影响

Effects of SB_(224289) on the pulmonary vascular smooth muscle cell proliferation induced by 5-HT

目的研究 5 HT1B受体拮抗剂SB2 2 42 89对 5 HT诱导的肺动脉平滑肌细胞增殖的影响 ,探讨肺血管构型重建的 5 HT1B受体机制。方法分离培养大鼠肺动脉平滑肌细胞 ,用MTT法和3 H TdR掺入法检测细胞增殖和DNA合成。结果SB2 2 42 89能剂量依赖地抑制 5 HT诱导的肺动脉平滑肌细胞增殖。SB2 2 42 89能剂量依赖地抑制 5 HT诱导的肺动脉平滑肌细胞的DNA合成 ,SB2 2 42 89能阻断 5 HT对肺动脉平滑肌细胞的促有丝分裂作用。结论SB2 2 42 89能抑制 5 HT引起的肺动脉平滑肌细胞的增殖。5 HT1B受体在 5 HT诱导的肺动脉平滑肌细胞增殖中有重要作用。

Objective To study the effects of SB_ 224289 ,a selective 5-HT_ 1B receptor antagonist on the pulmonary artery smooth muscle cells (PASMC) proliferation,investigate the role of the 5-HT_ 1B receptor in pulmonary remodeling.Methods PASMC was isolated from a rat′s pulmonary artery.The cultured PASMC was evaluated by the MTT assay and 3H-TdR incorporation.Results SB_ 224289 from 10 -10 ～10 -5 mol·L -1 dose-dependently inhibited the PASMC proliferation induced by 5-HT.The increase rates(%) were 166.6± 20.8,152.4±23.9,134.3±23.2,117.6±23.9,93.1±19.0,78.1±20.8 respectively.The increase rate(%) of the control was 193.7±9.7.SB_ 224289 from 10 -9 mol·L -1 to 10 -7 mol·L -1 dose-dependently inhibited the increase of PASMC 3H-TdR incorporation induced by 5-HT.The cpms were 7 341.0 ±95.0, 6 551.5 ±414.6 and 5 046.5 ±735.4 respectively.The inhibition of SB_ 224289 on the PASMC proliferation indicated that the mitogenesis effect of 5-HT on PASMC might be mediated by 5-HT_ 1B receptors.Conclusions SB_ 224289 blocked the PASMC mitogenesis induced by 5-HT.5-HT_ 1B receptors play very important roles in the PASMC proliferation and pulmonary remodeling.