质子泵抑制剂通过激活钙调神经磷酸酶诱发血管内皮炎症
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国家自然科学基金面上项目(81673515);江苏省自然科学基金面上项目(BK20161591);江苏省“六大人才高峰”项目(2014?YY?001);江苏省药学会奥赛康医院药学基金(A201615);苏州市产业技术创新专项(SYSD2016046);苏州市“科教兴卫”青年科技项目(KJXW2016067)


Proton pump inhibitor induce vascular endothelium inflammation by activating calcineurin
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    摘要:

    目的:研究质子泵抑制剂对人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)黏附和炎症水平的潜在影响及相关机制。方法:以10 μmol/L的兰索拉唑孵育HUVEC不同时间(0、24、48、72、96 h)后,应用qRT-PCR及Western blot技术检测细胞炎症因子白介素6(interleukin 6,IL-6)、细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)和血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)的蛋白及mRNA表达水平,同时检测HUVEC中钙调神经磷酸酶(calcineurin,CaN)及活化T细胞核因子(nuclear factor of activated T cell,NFAT)蛋白水平的变化。此外,用兰索拉唑及CaN抑制剂FK506单独或联合孵育细胞96 h后,检测HUVEC中NFAT、IL-6、ICAM-1及VCAM-1蛋白的表达情况。结果:兰索拉唑可以时间依赖性地增加HUVEC中CaN的表达和NFAT的核转位,并进一步增加IL-6、ICAM-1及VCAM-1的表达。CaN抑制剂可以很大程度上减轻兰索拉唑诱导这种效应。结论:兰索拉唑会诱发血管炎症并增加细胞黏附,其机制可能与CaN的活化有关。

    Abstract:

    Objective:This study aims to investigate the effect of proton pump inhibitors on adhesion and inflammation of human umbilical vein endothelial cells(HUVEC)and its potential mechanism. Methods:Western blot and qRT-PCR were used to detect the mRNA and protein expression of interleukin-6(IL-6),intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)in HUVECs after treating with 10 μmol/L lansoprazole for 0,24,48,72 and 96 h,protein levels of calcineurin(CaN)and nuclear factor of activated T cells(NFAT)were evaluated at the same time. In addition,protein levels of NFAT,IL-6,ICAM-1 and VCAM-1 were evaluated after treating with lansoprazole,CaN inhibitor FK506,and lansoprazole combined FK506 for the further research in mechanism. Results:Lansoprazole could time-dependently increase the expression of CaN and nuclear translocation of NFAT,and further increase the expression of IL-6,ICAM-1 amd VCAM-1. Calcineurin inhibitor could relieve the NFAT nuclear translocation and vascular inflammation induced by lansoprazole. Conclusion:Lansoprazole may induce endothelial cell inflammation and increase cell adhesion by activating CaN.

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张何坚,柏 蓉,鲍丽琴,张学会,孙鲁宁,马梦圆,程紫萍,陈安九,王永庆.质子泵抑制剂通过激活钙调神经磷酸酶诱发血管内皮炎症[J].南京医科大学学报(自然科学版),2021,(2):173-180

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  • 收稿日期:2019-10-27
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  • 在线发布日期: 2021-03-10
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