兰索拉唑致皮肤炎症的机制研究
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国家自然科学基金(81673515);江苏省自然科学基金(BK20161591)


Study on the mechanism of cutaneous inflammation induced by lansoprazole
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    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HE染色和免疫组化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后人永生化角质形成细胞(HaCaT)活力的变化,并用10、20、40 μmol/L的兰索拉唑分别孵育HaCaT 24 h、48 h,Western blot检测HaCaT中磷酸化核因子(NF)-κB蛋白(phospho-NF-κB p65,P-p65)的表达水平,同时检测细胞炎症因子白介素(interleukin,IL)-6、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 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(IL)-6 and 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 experiment 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.

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马梦圆,程紫萍,孙鲁宁,钱徐萍,孙诗钰,王 雨,陈安九,王永庆.兰索拉唑致皮肤炎症的机制研究[J].南京医科大学学报(自然科学版),2022,42(2):178-183

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  • 收稿日期:2021-11-13
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  • 在线发布日期: 2022-03-01
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