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·药学研究·


          芒果苷对心肌细胞损伤的保护作用及对NFATc4表达的影响
                                                                                                      Δ

          韦啟球 ,高 思,冯艺萍,裴世成,刘雪萍(广西科技大学医学部药学系,广西 柳州 545005)
                *
                                                #
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)20-2454-05
          DOI  10.6039/j.issn.1001-0408.2023.20.02

          摘   要  目的  研究芒果苷对过氧化氢(H2O2 )诱导的心肌细胞氧化应激损伤的保护作用,以及对活化T细胞核因子c4(NFATc4)表
          达的影响。方法  体外培养心肌H9c2细胞,分为空白组、H2O2组和芒果苷50、100、150 μmol/L组,芒果苷组细胞在经不同浓度芒果
          苷作用 12 h 后,再与 H2O2组一同经 H2O2 (200 μmol/L)刺激 12 h,检测各组细胞的相对存活率,细胞上清液中超氧化物歧化酶
         (SOD)、过氧化氢酶(CAT)、丙二醛(MDA)水平,细胞中活性氧(ROS)水平,以及细胞中凋亡相关蛋白[B 细胞淋巴瘤 2(Bcl-2)、
          Bcl-2 相关 X 蛋白(Bax)、剪切的胱天蛋白酶 3(cleaved caspase-3)]、核蛋白 NFATc4 的表达情况。转染 NFATc4 干扰序列,考察
          NFATc4对H2O2诱导的心肌细胞中氧化应激指标和凋亡相关蛋白的影响。结果  与空白组比较,H2O2组细胞的相对存活率,SOD、
          CAT水平,Bcl-2的相对表达量均显著降低;MDA、ROS水平,Bax、cleaved caspase-3和核蛋白NFATc4的相对表达量均显著升高(P<
          0.05或P<0.01)。与H2O2组比较,芒果苷100、150 μmol/L组细胞的上述指标均得以显著逆转(P<0.05)。转染NFATc4干扰序列后,
          核蛋白NFATc4的表达显著下调,MDA、ROS水平和Bax、cleaved caspase-3蛋白的表达均较H2O2组显著降低/下调,SOD、CAT水平和
          Bcl-2蛋白的表达均较H2O2组显著升高/上调(P<0.05)。结论  芒果苷能够减轻H2O2诱导的H9c2细胞氧化应激,减少细胞凋亡,抑制
          NFATc4蛋白入核,进而缓解心肌细胞损伤;降低NFATc4蛋白的核内水平与减轻H2O2诱导的氧化应激、细胞凋亡有关。
          关键词  芒果苷;H9c2细胞;氧化应激;凋亡;活化T细胞核因子c4

          Protective effects of mangiferin against myocardial cell damage and its effects on the expression of NFATc4
          WEI Qiqiu,GAO Si,FENG Yiping,PEI Shicheng,LIU Xueping(Dept.  of  Pharmacy,  School  of  Medicine,
          Guangxi University of Science and Technology, Guangxi Liuzhou 545005, China)

          ABSTRACT    OBJECTIVE  To  study  the  protective  effects  of  mangiferin  against  oxidative  stress  injury  of  myocardial  cells
          induced by hydrogen peroxide (H2O2 ), and its effects on the expression of nuclear factor of activated T cell cytoplasmic 4(NFATc4).
          METHODS  H9c2  myocardial  cells  were  cultured  in  vitro  and  divided  into  blank  group,  H2O2 group,  and  50,  100,  150  μmol/L
          mangiferin groups. Mangiferin groups were treated with different concentrations of mangiferin for 12 h, and then were subjected to
          H2O2 (200  μmol/L)  stimulation  for  12  hours  together  with  the  H2O2  group;  relative  survival  rate  was  detected  in  each  group,  and
          the  levels  of  superoxide  dismutase (SOD),  catalase (CAT)  and  malondialdehyde (MDA)  in  cell  supernatant  and  reactive  oxygen
          species (ROS)  in  H9c2  cells  were  measured.  Meanwhile,  the  expressions  of  apoptosis-related  proteins  [B  cell  lymphoma  2 (Bcl-
          2), Bcl-2 associated X protein (Bax), cleaved caspase-3] and nuclear protein NFATc4 were determined. Furthermore, the NFATc4
          interference  sequence  was  transfected,  and  the  effects  of  NFATc4  on  oxidant  stress  indexes  and  apoptosis-related  proteins  in  H2O2-
          induced  myocardial  cells  were  investigated.  RESULTS  Compared  with  blank  group,  relative  cell  viability,  the  levels  of  SOD  and
          CAT,  relative  expression  of  Bcl-2  were  decreased  significantly,  while  the  levels  of  MDA  and  ROS,  relative  expressions  of  Bax,
          cleaved  caspase-3  and  nuclear  protein  NFATc4  were  increased  significantly (P<0.05  or  P<0.01).  Compared  with  the  H2O2 group,
          the  above  indexes  of  100  and  150  μmol/L  mangiferin  groups  were  reversed  significantly (P<0.05). After  the  transfection  of  the
          NFATc4 interference sequence, the expression of nuclear protein NFATc4 was down-regulated significantly; the levels of MDA and
          SOD,  the  protein  expressions  of  Bax  and  cleaved  caspase-3  were  all  decreased/down-regulated  significantly,  while  the  levels  of
          SOD  and  CAT,  and  the  protein  expression  of  Bcl-2  were  all  increased/up-regulated  significantly,  compared  with  H2O2  group (P<
          0.05).  CONCLUSIONS  Mangiferin  can  relieve  H2O2-induced  oxidative  stress  of  H9c2  cells,  reduce  the  apoptosis  and  inhibit  the
          nuclear  translocation  of  NFATc4,  thereby  alleviating  myocardial  cell  damage;  reducing  the  nuclear  level  of  NFATc4  protein  is
          related to reducing H2O2-induced oxidative stress and cell apoptosis.
                                                              KEYWORDS    mangiferin;  H9c2  cells;  oxidative  stress;
              Δ 基金项目 国家自然科学基金项目(No.82160059);广西自然科            apoptosis; nuclear factor of activated T cells cytoplasmic 4
          学基金项目(No.2020GXNSFAA259025);广西科技大学博士基金项目
         (No.131135)                                              持续的病理性心脏肥大最终可导致心力衰竭,而病
             *第一作者 讲师,硕士。研究方向:天然产物活性。E-mail:
                                                              理性心脏肥大的发生和发展被认为是多种复杂因素综
          315833134@qq.com                                                [1]
              # 通信作者 副研究员,博士。研究方向:心血管药理。E-mail:               合作用的结果 。目前,临床尚缺乏有效手段来延缓或
          100000774@gxust.edu.cn                              逆转心脏肥大向心力衰竭进展。研究发现,在慢性心力


          · 2454 ·    China Pharmacy  2023 Vol. 34  No. 20                            中国药房  2023年第34卷第20期
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