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韩静茵,王淑娟,贾仰民,干晓瑜.阿魏酸钠通过阻断NF-κB途径降低NALP3诱导的矽肺中成纤维细胞增殖韩静茵[J].浙江中西医结合杂志,2023,33(12):
阿魏酸钠通过阻断NF-κB途径降低NALP3诱导的矽肺中成纤维细胞增殖韩静茵
Sodium ferulate reduces NALP3-induced fibroblast proliferation in silicosis by blocking NF-κB pathway
投稿时间:2022-12-14  修订日期:2023-11-22
DOI:
中文关键词:  阿魏酸钠  矽肺  NF-κB  NALP3  成纤维细胞
英文关键词:Sodium ferulate  Silicosis  NF-κB  NALP3  fibroblast
基金项目:浙江省医药卫生科技计划项目
作者单位E-mail
韩静茵 杭州市红十字会医院 1105406439@qq.com 
王淑娟 浙江大学医学院附属杭州市胸科医院  
贾仰民   
干晓瑜   
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中文摘要:
      目的 探讨阿魏酸钠对NALP3诱导的矽肺模型小鼠中成纤维细胞增殖影响的内在分子机制。方法 采用C57BL/6雄性小鼠建立矽肺模型,提取肺成纤维细胞,采用阿魏酸钠和Prostratin处理,并转染shNALP3载体。采用MTT检测细胞活力、Edu实验检测细胞增殖、ELISA检测caspase-1和IL-1β的活性;QRT-PCR检测NALP3表达,以及Western blotting检测NF-κB通路相关蛋白(p65、IkB、NALP3、collagen-1和α-SMA)表达量。结果 阿魏酸钠能够抑制p65、IkB、NALP3、collagen-1和α-SMA的表达,prostratin逆转阿魏酸钠抑制的细胞活力和增殖,同时逆转阿魏酸钠阻断的NF-κB通路蛋白表达和降低NALP3表达,以及逆转阿魏酸钠抑制的Caspase-1和IL-1β活性。转染shNALP3的细胞中NALP3含量明显低于阴性对照组;Prostratin促进的细胞活力和增殖受到shNALP3的逆转,沉默NALP3的细胞中caspase-1、IL-1β、collagen-1和α-SMA的活性明显被抑制,且逆转Prostratin促进caspase-1、IL-1β、collagen-1和α-SMA活性的作用。结论 阿魏酸钠通过阻断NF-κB途径降低NALP3诱导的矽肺中成纤维细胞增殖。
英文摘要:
      Objective To investigate the underlying molecular mechanism of the effect of sodium ferulate on the proliferation of fibroblasts in NALP3-induced silicosis model mice. Methods The silicosis model was established in C57BL/6 male mice, lung fibroblasts were extracted, treated with sodium ferulate and Prostratin, and transfected with shNALP3 vector. MTT was used to detect cell viability, Edu assay to detect cell proliferation, ELISA to detect the activities of caspase-1 and IL-1β; QRT-PCR to detect NALP3 expression, and Western blotting to detect NF-κB pathway-related proteins (p65, IkB, NALP3, collagen- 1 and α-SMA) expression levels. Result Sodium ferulate could inhibit the expression of p65, IkB, NALP3, collagen-1 and α-SMA, prostratin reverses the cell viability and proliferation inhibited by sodium ferulate, and reverses the expression of NF-κB pathway proteins blocked by sodium ferulate and decreased NALP3 expression, as well as reversal of sodium ferulate-suppressed the activity of Caspase-1 and IL-1β. The content of NALP3 in cells transfected with shNALP3 was significantly lower than that in the negative control group; the cell viability and proliferation promoted by Prostratin were reversed by shNALP3, and the activities of caspase-1, IL-1β, collagen-1 and α-SMA in cells that silenced NALP3 were significantly was inhibited and reversed the effect of Prostratin in promoting the activity of caspase-1, IL-1β, collagen-1 and α-SMA. Conclusion Sodium ferulate reduces NALP3-induced fibroblast proliferation in silicosis by blocking NF-κB pathway.
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