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黄芩素对缺氧致大鼠皮质神经元细胞损伤的保护作用及机制
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          张冬梅 ,张 洁,石志群,张朋朋,谭宏强,马慧萍(联勤保障部队第九四〇医院药剂科/全军高原医学实验室,
          兰州 730050)

          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)12-1431-06
          DOI  10.6039/j.issn.1001-0408.2023.12.05


          摘  要  目的  探讨黄芩素对缺氧致大鼠皮质神经元细胞损伤的保护作用及可能机制。方法  以大鼠皮质神经元RN-C细胞为研
          究对象,以缺氧条件(5%CO2、94%N2、1%O2 )培养24 h,考察不同浓度黄芩素(0.01、0.1、1、10、100 μmol/L)对缺氧RN-C细胞存活率
          的影响,并检测黄芩素(浓度为0.1 μmol/L)对缺氧细胞的乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,
          细胞迁移率、凋亡率和细胞周期,以及对缺氧细胞中活化的胱天蛋白酶3(cleaved caspase-3)、B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X
          蛋白(Bax)表达的影响。结果  与对照组比较,缺氧组细胞的存活率显著降低(P<0.01);0.01、0.1、1 μmol/L黄芩素可以逆转缺氧
          导致的细胞存活率降低(P<0.05或P<0.01)。划痕实验显示,黄芩素可显著升高缺氧RN-C细胞的迁移率(P<0.01)。与对照组
          比较,缺氧组细胞上清液中LDH活性、细胞中MDA含量、凋亡率和G1期细胞比例显著增加,SOD活性、G2+S期细胞比例显著降
          低(P<0.01);细胞中cleaved caspase-3蛋白的表达量显著上升,Bcl-2/Bax比值均显著下降(P<0.05或P<0.01)。与缺氧组比较,
          黄芩素组细胞显著逆转了上述指标(P<0.01)。结论  黄芩素能促进缺氧条件下大鼠皮质神经元细胞的增殖和迁移,改善缺氧诱
          导的细胞凋亡和细胞周期阻滞,降低上清液中LDH活性,降低细胞脂质过氧化水平,提高抗氧化水平;其机制可能与调控caspase-
          3/Bax/Bcl-2通路有关。
          关键词  黄芩素;大鼠皮质神经元细胞;缺氧;神经保护;caspase-3/Bax/Bcl-2

          Protective effect and mechanism of baicalein on hypoxia-induced cortical neuron injury in rats
          ZHANG Dongmei,ZHANG Jie,SHI Zhiqun,ZHANG Pengpeng,TAN Hongqiang,MA Huiping(Dept.  of
          Pharmacy, the 940th Hospital of Joint Logistics Support Force of PLA/Lab of PLA for High Altitude Medicine,
          Lanzhou 730050, China)

          ABSTRACT   OBJECTIVE  To  explore  the  protective  effect  and  possible  mechanism  of  baicalein  on  hypoxia-induced  cortical
          neuron  injury  in  rats.  METHODS  The  cortical  neurons  of  rats (RN-C  cells)  were  studied  and  cultured  under  hypoxic  conditions
         (5%CO2, 94% N2, 1%O2 ) for 24 hours; the effects of different concentrations of baicalein (0.01, 0.1, 1, 10, 100 μmol/L) on the
          survival  rate  of  hypoxic  RN-C  cells  were  investigated;  the  effects  of  baicalein (0.1  μmol/L)  on  the  activities  of  lactate
          dehydrogenase (LDH) and superoxide dismutase (SOD), the content of malondialdehyde (MDA), migration rate, apoptotic rate,
          cell  cycle  and  the  expressions  of  cleaved  caspase-3,  B-cell  lymphoma-2 (Bcl-2)  and  Bcl-2  X  protein (Bax)  were  all  detected.
          RESULTS  Compared  with  control  group,  the  survival  rate  of  cells  in  the  hypoxia  group  was  significantly  reduced (P<0.01);
          0.01,  0.1  and  1  μmol/L  baicalein  could  reverse  survival  rate  of  hypoxia-induced  cortical  neurons (P<0.05  or  P<0.01).  Scratch
          experiments  showed  that  baicalein  significantly  increased  the  migration  rate  of  hypoxic  RN-C  cells (P<0.01).  Compared  with
          control  group,  the  activity  of  LDH  in  the  supernatant  and  the  content  of  MDA  in  the  cells,  apoptotic  rate  and  the  proportion  of
          cells in G1 phase, were significantly increased in the hypoxia group, while SOD activity and the proportion of cells in G2+S phase
          was decreased significantly (P<0.01). The protein expressions of cleaved caspase-3 were increased significantly, while the ratio of
          Bcl-2/Bax  in  cells  was  significantly  reduced (P<0.05  or  P<0.01).  Compared  with  hypoxia  group,  the  above  indexes  were  all
          reversed  significantly  in  baicalein  group (P<0.01).  CONCLUSIONS  Baicalein  can  promote  the  proliferation  and  migration  of
          cortical  neurons,  improve  hypoxia-induced  cell  apoptosis  and  cell  cycle  distribution,  decrease  the  activity  of  LDH  in  supernatant
          and the level of cellular lipid peroxidation, and improve antioxidant levels. Its mechanism may be related to regulating the caspase-
          3/Bax/Bcl-2 pathway.
                                                             KEYWORDS     baicalein;  cortical  neuron  of  rats;  hypoxia;
             Δ 基金项目 甘肃省科技计划项目(No.22JR11RA014);甘肃省卫
                                                             neuroprotection; caspase-3/Bax/Bcl-2
          生健康行业科研项目(No.GSWSKY2022-46);第九四〇医院院内科研
          项目(No.2021yxky046,No.2022yxky004)
             *第一作者 主管药师,硕士。研究方向:高原缺氧损伤分子机制。                      大脑是机体对缺氧最敏感的器官,缺氧可引起神经
          E-mail:835935150@qq.com
                                                             元等许多其他细胞的损伤,导致机体学习记忆能力降
             # 通信作者 主任药师,教授,硕士生导师。研究方向:高原缺氧损
          伤机制及新药研发。E-mail:1026573411@qq.com                  低、智力发育迟缓等,因此减少缺氧引起的脑组织细胞


          中国药房  2023年第34卷第12期                                              China Pharmacy  2023 Vol. 34  No. 12    · 1431 ·
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