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目的 :研究新型磷酸二酯酶 3型抑制剂西洛他唑 (cilostazol)对TNF α诱导人脐静脉内皮细胞(HUVECs)释放可溶性细胞粘附分子 (sCAMs)的影响 ,并探讨其作用机制。方法 :体外培养第 4～ 6代HUVECs,以TNF α (10 μg·L-1)刺激细胞 ,并与西洛他唑 (1～ 10 μmol·L-1)共培养 2 4h ,取培养上清 ,通过ELISA法测定可溶性血管细胞粘附分子 1(sV CAM 1)、细胞间粘附分子 1(sICAM 1)以及E 选择素(sELAM 1,sE selectin) ,并以四唑蓝 (MTT)法考察细胞生长状态。结果 :1～ 10 μmol·L-1的西洛他唑对TNF α诱导的HUVECs释放sICAM 1和sE selectin无明显影响 ,但显著抑制sVCAM 1的生成 ,并且该作用被一种非选择性一氧化氮合成酶 (NOS)抑制剂Lω NAME(0 .1μmol·L-1)所阻断。MTT法测定结果显示 ,西洛他唑作用于HUVECs 2 4h ,低浓度(1μmol·L-1)可显著改善细胞生长状态 ;高浓度(30 μmol·L-1)表现为抑制 ,而中浓度 (10 μmol·L-1)对细胞生长状态几乎无影响。结论 :西洛他唑显著抑制由TNF α诱导的HUVECs释放sVCAM 1,该作用可能与激活NOS并通过NO依赖性通路介导有关 ,提示该药可在一定程度上对抗由细胞因子所引起的部分粘附反应 ,因此在动脉粥样硬化以及其它心血管疾病的治疗中具有潜在的应用价值
AIM: To investigate the effect of cilostazol, a novel phosphodiesterase type 3 inhibitor, on the release of soluble cell adhesion molecules (sCAMs) from human umbilical vein endothelial cells (HUVECs) induced by TNFα and its possible mechanism. Methods: HUVECs from the 4th to 6th passage were cultured in vitro and the cells were stimulated with TNFα (10 μg · L-1) for 24 hours. The cultured supernatants , SV CAM 1, sICAM 1 and sE selectin were detected by ELISA and examined by MTT method Cell growth status. Results: Cilostazol at 1 ~ 10 μmol·L -1 had no significant effect on the release of sICAM 1 and sE selectin from HUVECs induced by TNFα, but significantly inhibited the production of sVCAM 1, and this effect was inhibited by a nonselective monoxide Nitric synthase (NOS) inhibitor Lω NAME (0 1μmol·L-1) blocked. The results of MTT assay showed that cilostazol could inhibit the proliferation of HUVECs at 24 h and the low concentration of 1 μmol·L-1 could significantly inhibit the growth of HUVECs. The high concentration (30 μmol·L-1) 10 μmol·L-1) had almost no effect on cell growth. CONCLUSION: Cilostazol significantly inhibits the release of sVCAM-1 from HUVECs induced by TNFα, which may be related to the activation of NOS and mediated through NO-dependent pathway, suggesting that the drug may antagonize to some extent the cytokine-induced part Adhesion reaction, and therefore has potential value in the treatment of atherosclerosis and other cardiovascular diseases