Page 32 - 南京医科大学学报自然科学版

南京医科大学学报（自然科学版） 第42卷第2期
·178 · Journal of Nanjing Medical University（Natural Sciences） 2022年2月

·基础医学·

兰索拉唑致皮肤炎症的机制研究

马梦圆 ，程紫萍 ，孙鲁宁 ，钱徐萍 ，孙诗钰 ，王 雨 ，陈安九 ，王永庆 1，2，3*
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徐州医科大学江苏省新药研究与临床药学重点实验室，江苏 徐州 221004；南京医科大学第一附属医院药学部，江苏 南
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京 210029；南京医科大学药学院，江苏 南京 211166
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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。
［关键词］ 兰索拉唑；皮肤炎症；NF⁃κB信号通路；IL⁃6；IL⁃1β
［中图分类号］ R758.25 ［文献标志码］ A ［文章编号］ 1007⁃4368（2022）02⁃178⁃06
doi：10.7655/NYDXBNS20220205

Study on the mechanism of cutaneous inflammation induced by lansoprazole

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MA Mengyuan ，CHENG Ziping ，SUN Luning ，QIAN Xuping ，SUN Shiyu ，WANG Yu ，CHEN Anjiu ，WANG
Yongqing 1，2，3*
1 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy，Xuzhou Medical University，Xuzhou 221004；
Department of Pharmacy，the First Affiliated Hospital of Nanjing Medical University，Nanjing 210029；School of
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Pharmacy，Nanjing Medical University，Nanjing 211166，China
［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.
［Key words］ lansoprazole；cutaneous inflammation；NF⁃κB signaling pathway；IL⁃6；IL⁃1β
［J Nanjing Med Univ，2022，42（02）：178⁃183］
［基金项目］ 国家自然科学基金（81673515）；江苏省自然科学基金（BK20161591）
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通信作者（Corresponding author），E⁃mail：wyqjsph@163.com；wulynj@163.com