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目的:观察化合物Sanggenon C对人外周血多形核白细胞(PMN)与人滑膜细胞(HSC)粘附的抑制作用,并探讨其作用机制.方法:MTT比色法研究PMN与HSC粘附,Cell-ELISA及RT-PCR法研究HSC粘附分子ICAM-1和VCAM-1表达,EMSA研究核转录因子NF-κB的活化.结果:Sanggenon C在0.01-10μmol·L~(-1)范围内均可显著抑制TNF-α 5O kU·L~(-1)与IL-1β诱导的HSC与PMN粘附,其IC_(50)分别为27.29nmol. L~(-1)和54.45nmol·L~(-1);Sanggenon C可显著抑制HSC表面ICAM-1和VCAM-1蛋白表达,同时也显著抑制VCAM-1 mRNA表达,但对ICAM-1 mRNA表达无显著影响;Sanggenon C在1-10μmol·L~(-1)浓度下也可显著抑制TNF-α对NF-κB的活化.结论:Sanggenon C是一个有效的人PMN与HSC粘附抑制剂,其作用机制可能是通过抑制NF-κB的活化,进而抑制HSC表面VCAM-1的表达或抑制ICAM-1转录后调控过程而实现的.
OBJECTIVE: To observe the inhibitory effect of compound Sanggenon C on the adhesion of human peripheral blood polymorphonuclear leukocytes (PMN) and human synoviocytes (HSC), and to explore its mechanism.Methods: MTT assay was used to study the adhesion of PMN to HSC, The expression of ICAM-1 and VCAM-1 in HSC were detected by Cell-ELISA and RT-PCR, and the activation of NF-κB was detected by EMSA.Results: Sanggenon C was in the range of 0.01-10μmol·L -1 Could significantly inhibit the adhesion of HSC and PMN induced by TNF-α 5O kU · L -1 and IL-1β with IC 50 of 27.29 nmol L -1 and 54.45 nmol·L -1, (-1). Sanggenon C could significantly inhibit the expression of ICAM-1 and VCAM-1 on HSC surface as well as inhibit the expression of VCAM-1 mRNA, but had no significant effect on the expression of ICAM-1 mRNA. L ~ (-1) could also significantly inhibit the activation of NF-κB by TNF-α.Conclusion: Sanggenon C is a potent inhibitor of human PMN and HSC adhesion, and its mechanism may be through inhibition of NF-κB Activation, and then inhibit the expression of VCAM-1 on the HSC surface or inhibit the post-transcriptional regulation of ICAM-1.