【摘要】 背景分形趋化因子通过介导炎症细胞的趋化与血管内皮损伤相关,阿司匹林具有抗炎作用,抑制多种细胞因子表达,其对分形趋化因子的影响尚无报道。目的探讨阿司匹林对肿瘤坏死因子α(TNF-α)刺激的人脐静脉内皮细胞(HUVEC)分形趋化因子表达的影响和作用机制。方法将 HUVEC 随机分为:空白组(无TNF-α刺激和药物干预),TNF-α刺激组,TNF-α+PDTC 干预组(PI)TC 系核因子 kB 的特异性活性抑制剂),TNF-α+NS398干预组(NS398是 COX-2的特异性活性抑制剂)。TNF-α+阿司匹林0.02 mol/L 干预组,TNF-α+阿司匹林0.2 mol/L,干预组,TNF-α+阿司匹林1 mol/L 干预组,TNF-α+阿司匹林5 mol/L 干预组,共8组,每组3例。分别用 RT-PCR 法和 Western blot 法检测各组细胞分形趋化因子(分形素)和核因子 kB p65(NF-kBp65)的 mRNA 水平和蛋白表达。结果 1)4μg/L TNF-α使 HUVEC 的分形趋化因子 mRNA 水平和蛋白表达明显增加(P<0.01)。2)阿司匹林浓度依赖性抑制 TNF-α诱导的 HUVEC 分形趋化因子 mRNA 水平和蛋白表达(P<0.01);阿司匹林浓度依赖性地抑制 HUVEC 的 NF-kB p65 mRNA 水平和蛋白表达(P<0.01)。3)PDTC抑制 TNF-α诱导的 HUVEC 分形趋化因子 mRNA 水平和蛋白表达(均 P<0.01)。结论阿司匹林通过 NF-kBp65途径抑制 TNF-α诱导的 HUVEC 分形趋化因子 mRNA 水平和蛋白表达,并可能借此发挥抗动脉粥样硬化作用。更多还原

【Abstract】 Background Fractalkine is involved in the impairment of endothelium by mediating inflammatory cell chemotaxis.Aspirin inhibites many kinds of cytokine expression.Objective To investigate the effect of aspirin on tumor necrosis factor α(TNF-α) stimulated fractalkine expression in human umbilical vein endothelial cells (HUVEC) and its mechanism.Methods HUVEC were grouped as follows:control group;TNF-α-stimu- lated;TNF-α+NS-398;TNF-α+PDTC and TNF plus various concentration of aspirin (0.02,0.2,1.5 mmol/L). The level of mRNA and protein expression of fractalkine and nuclear factor(NF)-kB p65 was determined by RT- PCR and Western blot.Results 1)Fractalkine mRNA and protein level was increased after 4 μg/L TNF-α stim- ulation in HUVEC(both P<0.01).2)TNF-α-stimulated fractalkine mRNA and protein expression was sup- pressed by aspirin in a dose dependent manner(both P<0.01).Concurrently,NF-kB p65 mRNA and protein expression was suppressed by aspirin in a dose-dependent manner(All P<0.01)as well.3)PDTC a specific in- hibitor of NF-kB prevent the TNF α stimulated fractalkine mRNA and protein expression (both P<0.01). Conclusion Aspirin suppresses the TNF-α-stimulated expression in HUVEC mediating NF-kB p65 pathway.更多还原