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目的通过观察红霉素衍生物9(S)-羟基红霉素对活化T淋巴细胞核转录因子(NF)-κB表达的影响,探讨红霉素衍生物在RA治疗中的潜在意义。方法事先加入不同剂量的红霉素或9(S)-羟基红霉素后,用肿瘤坏死因子(TNF)-α诱导活化T淋巴细胞NF-κB表达,体外培养1h后,利用反转录-聚合酶链反应(RT-PCR)方法观察上述化合物对NF-κB的mRNA表达影响,利用Western Blot方法观察上述化合物对NF-κB蛋白水平表达的影响。结果红霉素和9(S)-羟基红霉素均可抑制活化T淋巴细胞NF-κB的mRNA和蛋白表达。并与剂量呈相关性,在100μg/ml时红霉素和9(S)-羟基红霉素使NF-κB mRNA的相对表达分别降低36%、45%(P<0.01),使蛋白表达分别降低46%,56%(P<0.01)。结论红霉素及其衍生物的抗炎活性可能是通过对活化T淋巴细胞NF-κB信号途径的作用实现的,提示红霉素衍生物在类风湿关节炎治疗中具有潜在意义。
Objective To investigate the potential role of erythromycin derivatives in the treatment of RA by observing the effect of erythromycin derivative 9 (S) -hydroxy erythromycin on the expression of nuclear transcription factor (NF) -κB in activated T lymphocytes. Methods After pretreatment with different dosages of erythromycin and 9 (S) -hydroxys erythromycin, the expression of NF-κB in activated T lymphocytes was induced by tumor necrosis factor (TNF) -α. After cultured for 1 h in vitro, The effects of the above compounds on the mRNA expression of NF-κB were observed by polymerase chain reaction (RT-PCR). The effects of these compounds on the expression of NF-κB protein were observed by Western Blot. Results Both erythromycin and 9 (S) -hydrox erythromycin could inhibit the mRNA and protein expression of NF-κB in activated T lymphocytes. The results showed that erythromycin and 9 (S) -hydroxy erythromycin decreased the relative expression of NF-κB mRNA by 36% and 45% (P <0.01) at 100μg / ml respectively, Decreased by 46% and 56% (P <0.01). Conclusion The anti-inflammatory activity of erythromycin and its derivatives may be through the activation of NF-κB signaling pathway in activated T lymphocytes, suggesting that erythromycin derivatives have potential significance in the treatment of rheumatoid arthritis.