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·药学研究·


          孪药 ST-11 对氧糖剥夺/再灌注致 PC12 细胞损伤的保护作用及
          机制     Δ



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          文金兰 ,陈莉娜 ,张善惠 ,鲁 俊 ,吴淑霞 ,张金娟 ,董永喜 ,董 莉 (1. 贵州医科大学药学院,贵阳
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          550025;2.贵州医科大学基础医学院,贵阳 550025)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)06-0660-06
          DOI  10.6039/j.issn.1001-0408.2023.06.04
          摘   要  目的  研究川芎嗪-灯盏乙素苷元孪药ST-11对氧糖剥夺/再灌注(OGD/R)致大鼠肾上腺髓质嗜铬细胞瘤PC12细胞损伤
          的保护作用及机制。方法  将细胞分为空白组、模型组、尼莫地平组(阳性对照,5 μmol/L)、ST-11不同浓度组(5、10、20 μmol/L)。
          预先给药干预24 h后,除空白组外的其余各组细胞均以含10 mmol/L Na2S2O4的无糖DMEM培养基缺糖缺氧培养4 h,待复糖复氧
          培养4 h后,检测各组细胞的存活率,细胞上清液中乳酸脱氢酶(LDH)、过氧化氢酶(CAT)、谷胱甘肽(GSH)、丙二醛(MDA)、超氧
          化物歧化酶(SOD)的含量,细胞凋亡率,细胞活性氧(ROS)和线粒体膜电位(MMP)水平,以及B细胞淋巴瘤2相关X蛋白(Bax)、
          B细胞淋巴瘤2(Bcl-2)及胱天蛋白酶3(caspase-3)蛋白的表达情况。结果  与空白组比较,模型组的细胞存活率,上清液中CAT、
          GSH和SOD含量,细胞MMP水平,细胞Bcl-2蛋白的相对表达量和Bcl-2/Bax比值均显著降低(P<0.05),而上清液中LDH、MDA
          含量,细胞ROS 水平,细胞凋亡率,细胞 Bax、caspase-3 蛋白的相对表达量均显著升高(P<0.05)。与模型组比较,ST-11 各浓度
          组上述指标(5 μmol/L ST-11组caspase-3蛋白除外)均显著逆转(P<0.05)。结论  ST-11对OGD/R致PC12细胞损伤具有一定的保
          护作用,且作用可能与减少细胞氧化应激、抑制细胞凋亡有关。
          关键词  ST-11;川芎嗪;灯盏乙素苷元;孪药;氧糖剥夺/再灌注;氧化应激;细胞凋亡;PC12细胞

          Protective  effects  of  twin  drug  ST-11  against  PC12  cell  injury  induced  by  oxygen-glucose  deprivation/
          reperfusion and its mechanism
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          WEN Jinlan ,CHEN Lina ,ZHANG Shanhui ,LU Jun ,WU Shuxia ,ZHANG Jinjuan ,DONG Yongxi ,
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          DONG Li(1.  School  of  Pharmacy,  Guizhou  Medical  University,  Guiyang  550025,  China;2.  School  of  Basic
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          Medicine, Guizhou Medical University, Guiyang 550025, China)
          ABSTRACT    OBJECTIVE  To  study  the  protective  effects  of  ligustrazine-scutellarein  twin  drug  ST-11  on  rat  adrenal  medullary
          pheochromocytoma  PC12  cell  injury  induced  by  oxygen-glucose  deprivation/reperfusion (OGD/R)  and  its  mechanism.  METHODS
          PC12  cells  were  divided  into  blank  group,  model  group,  nimodipine  group (positive  control,  5  μmol/L)  and  different
          concentration  groups  of  ST-11 (5,  10,  20  μmol/L). After  24  hours  of  pre-administration  intervention,  all  the  other  groups  except
          the  blank  group  were  cultured  in  glucose-free  DMEM  culture  medium  containing  10  mmol/L  Na2S2O4  for  4  hours  with  glucose
          deficiency and hypoxia. After 4 hours of glucose and oxygen re-introduction, the survival rate of cells in each group, the contents
          of  lactate  dehydrogenase (LDH),  catalase (CAT),  glutathione (GSH),  malondialdehyde (MDA)  and  superoxide  dismutase
         (SOD)  in  cell  supernatant,  apoptosis  rate,  the  levels  of  reactive  oxygen  species (ROS)  and  mitochondrial  membrane  potential
         (MMP),  the  protein  expressions  of  B-cell  lymphoma  2  related  X  protein (Bax),  B-cell  lymphoma  2 (Bcl-2)  and  caspase-3  were
          all detected in each group. RESULTS Compared with blank group, the cell survival rate, the contents of CAT, GSH and SOD in
          cell  supernatant,  MMP  level,  relative  expression  of  Bcl-2  and  Bcl-2/Bax  ratio  in  model  group  decreased  significantly (P<0.05),
          while  the  contents  of  LDH  and  MDA,  ROS  level,  apoptosis  rate,  relative  expressions  of  Bax  and  caspase-3  were  significantly
                                                              increased (P<0.05).  Compared  with  model  group,  above
              Δ 基金项目 国家自然科学基金资助项目(No.81960630);国家级
                                                              indexes  of  ST-11  groups (except  for  the  protein  expression  of
          大学生创新创业训练计划项目(No.202010660029);贵州省普通高等
                                                              caspase-3  in  5  μmol/L  ST-11  group)  were  reversed  signifi-
          学校青年科技人才成长项目(No.黔教合KY字〔2021〕164);贵州省卫
                                                              cantly (P<0.05). CONCLUSIONS ST-11 has a certain protec-
          生健康委员会科学技术基金项目(No.gzwkj2021-448);贵州医科大学学
                                                              tive  effect  on  OGD/R-injured  PC12  cells,  and  its  effects  may
          术新苗培养及创新探索专项项目(No.黔科合平台人才〔2018〕5779-65)
             *第一作者 硕士研究生。研究方向:中药药效及毒理机制。电                     be related to reduction of oxidative stress and inhibition of cell
          话:0851-88416153。E-mail:1372389145@qq.com            apoptosis.
              # 通信作者 副教授,硕士生导师,博士。研究方向:中药药效学、                 KEYWORDS    ST-11;  ligustrazine;  scutellarein;  twin  drug;
          药理学和安全性评价。电话:0851-88416153。E-mail:108405755@qq.     oxygen-glucose  deprivation/reperfusion;  oxidative  stress;  cell
          com                                                 apoptosis; PC12 cells


          · 660 ·    China Pharmacy  2023 Vol. 34  No. 6                               中国药房  2023年第34卷第6期
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