化合物1487B抑制肿瘤坏死因子-α生成机制研究

发布时间：2018-06-12 06:45

本文选题：新化合物 + B　；参考：《中国药学杂志》2015年20期

【摘要】：目的研究化合物1487B对肿瘤坏死因子-α(TNF-α)的作用,探讨其抗炎机制。方法利用荧光标记底物,检测在不同浓度化合物1487B作用下,THP-1细胞中肿瘤坏死因子-α转化酶(TACE)的活性;采用实时定量PCR法,分析肿瘤坏死因子-α的转录水平;利用酶联免疫吸附实验及免疫印迹,测定肿瘤坏死因子-α的分泌表达水平。结果在THP-1细胞中,1487B对胞内TACE酶活性有一定的抑制作用,实时定量PCR检测1487B可降低肿瘤坏死因子-α转录,且呈明显的剂量依赖性;免疫印迹及酶联免疫吸附实验检测终浓度为50、100、200μmol·L-1的1487B作用THP-1细胞后,肿瘤坏死因子-α前体的表达减少63%(P0.01)、72%(P0.01)、67%(P0.01),肿瘤坏死因子-α的分泌水平降低24%(P0.05)、31%(P0.01)、70%(P0.001)。结论 1487B通过抑制THP-1细胞胞内TACE酶活性和肿瘤坏死因子-α转录,减少肿瘤坏死因子-α生成,本实验初步阐明了化合物1487B的抗炎机制,为其进一步应用奠定了基础。
[Abstract]:Objective to study the effect of compound 1487B on tumor necrosis factor- 伪 (TNF- 伪) and its anti-inflammatory mechanism. Methods the activity of tumor necrosis factor- 伪 invertase (TNF- 伪) in THP-1 cells was detected by fluorescence labeled substrates, and the transcription level of TNF- 伪 was analyzed by real-time quantitative PCR. The secretory expression of tumor necrosis factor-伪 was determined by enzyme linked immunosorbent assay (Elisa) and Western blot. Results the activity of TACE in THP-1 cells was inhibited by 1487B, and the expression of tumor necrosis factor- 伪 was decreased by real-time quantitative PCR in a dose-dependent manner. Immunoblotting and enzyme-linked immunosorbent assay (Elisa) showed that the expression of tumor necrosis factor- 伪 precursor in THP-1 cells was decreased by 50100200 渭 mol L-1 1487B, and the expression of tumor necrosis factor- 伪 precursor was reduced by 63% P0.01P0.01 + 77.01%, and the secretion level of TNF- 伪 was decreased by P0.0531P0.01P0.001 ~ (-1). Conclusion 1487B can reduce the production of tumor necrosis factor- 伪 by inhibiting the activity of TACE and the transcription of tumor necrosis factor- 伪 in THP-1 cells. In this study, the anti-inflammatory mechanism of compound 1487B was preliminarily elucidated, which laid a foundation for its further application.
【作者单位】：中国医学科学院北京协和医学院医药生物技术研究所卫生部抗生素生物工程重点实验室;
【基金】：国家自然科学基金资助项目(31070086) 北京协和医学院协和青年科研基金资助项目(33320140093)
【分类号】：R96

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