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南京医科大学学报(自然科学版)                                  第42卷第6期
               ·802 ·                     Journal of Nanjing Medical University(Natural Sciences)   2022年6月


             ·基础研究·

              兰索拉唑诱导心肌细胞氧化应激损伤的机制研究



              钱徐萍 ,张学会 ,孙鲁宁 ,王              雨 ,孙诗钰 ,马梦圆 ,程紫萍 ,陈安九 ,王永庆                  1,2*
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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
              1                                                           2
              京 210029;江苏盛泽医院药学部,江苏 苏州              215228
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             [摘    要] 目的:探索兰索拉唑(lansoprazole,LPZ)对大鼠心肌细胞 H9C2 的潜在损伤效应及相关机制。方法:以 10 μmol/L
              LPZ 孵育 H9C2 细胞不同时间(0 h、12 h、24 h、48 h)后,采用 DCFH⁃DA 荧光探针检测细胞内活性氧(reactive oxygen species,
              ROS)水平,Western blot 检测内质网应激蛋白(GRP78、CHOP)及凋亡相关蛋白(Cleaved⁃Caspase⁃12、Cleaved⁃Caspase⁃3、Cyt C、
              Bax/Bcl⁃2)的表达。此外,兰索拉唑及ROS抑制剂N⁃乙酰⁃L⁃半胱氨酸(N⁃acetyl⁃L⁃cysteine,NAC)单独或联合孵育细胞48 h后,
              检测H9C2细胞内ROS水平,以及内质网应激和凋亡相关蛋白的表达情况。结果:LPZ可以时间依赖性增加ROS的水平,诱导
              GRP78和CHOP的表达,并进一步增加Cleaved⁃Caspase⁃12、Cleaved⁃Caspase⁃3、Cyt C、Bax/Bcl⁃2的表达。NAC显著降低LPZ诱
              导的 ROS 水平,降低 GRP78、CHOP 以及 Cleaved⁃Caspase⁃12、Cleaved⁃Caspase⁃3、Cyt C、Bax/Bcl⁃2 的表达水平。结论:LPZ 可诱
              导心肌细胞凋亡,机制可能与氧化应激和内质网应激有关。
             [关键词] 兰索拉唑;大鼠心肌细胞;氧化应激;活性氧;内质网应激
             [中图分类号] R965                      [文献标志码] A                       [文章编号] 1007⁃4368(2022)06⁃802⁃07
              doi:10.7655/NYDXBNS20220606


              Mechanism of lansoprazole inducing oxidative stress injury in myocardial cells

              QIAN Xuping ,ZHANG Xuehui ,SUN Luning ,WANG Yu ,SUN Shiyu ,MA Mengyuan ,CHENG Ziping ,
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              CHEN Anjiu ,WANG Yongqing  1,2*
              1 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou 221004;
              2 Department of Pharmacy,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029;Department
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              of Pharmacy,Jiangsu Shengze Hospital,Suzhou 215228,China
             [Abstract] Objective:This study aims to explore the potential damage effect and related mechanisms of lansoprazole(LPZ)on rat
              cardiomyocytes(H9C2). Methods:After incubating H9C2 cells with 10 μmol/L LPZ for 0 h,12 h,24 hand 48 h,DCFH ⁃ DA
              fluorescent probe was used to detect the level of reactive oxygen species(ROS). And the expression of endoplasmic reticulum
              stressproteins(GRP78,CHOP)and apoptosis ⁃ related proteins(Cleaved ⁃ Caspase ⁃ 12,Cleaved ⁃ Caspase ⁃ 3,Cyt C,Bax/Bcl ⁃ 2)was
              detected by Western blot. In addition,the level of ROS,as well as the expression of endoplasmic reticulum stress and apoptosis⁃related
              proteins were evaluated after H9C2 cells incubating with LPZ alone or in combination with ROS inhibitor N⁃Acetyl⁃L⁃cysteine(NAC)
              for 48 h. Results:Lansoprazole could time⁃dependently increase the level of ROS,induce the expression of GRP78 and CHOP,and
              further increase the expression of Cleaved⁃Caspase⁃12,Cleaved⁃Caspase⁃3,Cyt C,and Bax/Bcl⁃2. NAC significantly reduced LPZ⁃
              induced ROS levels,and decreased the expression levels of GRP78,CHOP,Cleaved⁃Caspase⁃12,Cleaved⁃Caspase⁃3,Cyt C and Bax/
              Bcl⁃2. Conclusion:LPZ could induce cardiomyocyte apoptosis,and the mechanism may be related to oxidative stress and endoplasmic
              reticulum stress.
             [Key words] lansoprazole;rat cardiomyocytes;oxidative stress;ROS;endoplasmic reticulum stress
                                                                            [J Nanjing Med Univ,2022,42(06):802⁃808]





             [基金项目] 国家自然科学基金(81673515);江苏省自然科学基金(BK20161591)
              ∗
              通信作者(Corresponding author),E⁃mail:wyqjsph@163.com;wulynj@163.com
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