兰索拉唑致皮肤炎症的机制研究
DOI:
作者:
作者单位:

1.徐州医科大学江苏省新药研究与临床药学重点实验室;2.南京医科大学第一附属医院;3.徐州医科大学

作者简介:

通讯作者:

中图分类号:

基金项目:

国家自然科学基金项目(面上项目,重点项目,重大项目)


Study on the mechanism of cutaneous inflammation induced by lansoprazole
Author:
Affiliation:

1.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University;2.Department of Pharmacy, the First Affiliated Hospital of Nanjing Medical University

Fund Project:

The National Natural Science Foundation of China (General Program, Key Program, Major Research Plan)

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    目的:通过体内实验和体外实验探索兰索拉唑诱发皮肤炎症的可能机制。方法:体内实验,小鼠连续灌胃给药6个月,通过苏木精-伊红染色(HE染色)和免疫组化(IHC)评价小鼠皮肤组织损伤情况;体外实验,通过CCK-8测定10-200 μmol/L兰索拉唑孵育24 h和48 h后HacaT细胞活力的变化,并用10 μmol/L、20 μmol/L、40 μmol/L的兰索拉唑分别孵育HacaT细胞24 h、48 h,Western blot检测HacaT中NF-κB蛋白的磷酸化水平,同时检测细胞炎症因子白介素6(Interleukin 6,IL-6)、白介素1β(Interleukin 1β,IL-1β)的蛋白表达量。此外,兰索拉唑及NF-κB通路抑制剂吡咯烷二硫代甲酸铵(Pyrrolidine dithiocarbamate,PDTC)单独或联合孵育HacaT 细胞24 h、48 h后,检测HacaT中P-p65、IL-6和IL-1β蛋白的表达情况。结果:体内实验结果显示,兰索拉唑可造成小鼠皮肤损伤;体外实验发现,兰索拉唑可降低细胞活力,增加P-p65蛋白的表达,介导NF-κB通路激活,进一步刺激炎症因子IL-6和IL-1β的表达。PDTC可抑制兰索拉唑介导的NF-κB通路的激活,减少炎症因子的表达。结论:兰索拉唑可以促进炎症因子表达继而诱发皮肤损伤,其机制可能与NF-κB信号通路的激活有关。

    Abstract:

    Objective: This study aims to investigate the mechanism of lansoprazole on skin inflammation through in vivo and in vitro experiments. Methods: In vivo experiment, mice were given continuous gavage for 6 months. The skin tissue damage of mice was evaluated and analyzed by hematoxylin-eosin staining (HE staining) and immunohistochemistry (IHC). In vitro experiment, CCK-8 was used to determine the changes of HaCaT cell viability after incubation with 10-200 μmol/L lansoprazole for 24 h and 48 h. After incubation with 10 μmol/L, 20 μmol/L and 40 μmol/L lansoprazole for 24 h and 48 h, respectively, the phosphorylation levels of NF-κB in HacaT cells and the protein expressions of interleukin 6 (IL-6) and interleukin 1β (IL-1β) in HacaT cells were detected by Western blot. In addition, the protein expressions of P-p65, IL-6 and IL-1β in HacaT cells were detected after 24 h and 48 h incubation of HacaT cells with pyrrolidine dithiocarbamate, an inhibitor of NF-κB signaling pathway, alone or in combination with lansoprazole. Results: In vivo experiments showed that lansoprazole can cause skin damage in mice. In vitro studies found that lansoprazole can decrease cell viability, increase the expression of P-p65 proteins, mediate the activation of the pathway, and further stimulate the expression of inflammatory cytokines IL-6 and IL-1β. PDTC can inhibit the lansoprazole-mediated activation of NF-κB pathway and reduce the expression of inflammatory factors. Conclusion: Lansoprazole can promote the expression of inflammatory factors and induce skin injury, and the mechanism may be related to the activation of NF-κB signaling pathway.

    参考文献
    相似文献
    引证文献
引用本文
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2021-04-25
  • 最后修改日期:2021-06-17
  • 录用日期:2022-02-25
  • 在线发布日期:
  • 出版日期: