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芒柄花素对脂多糖诱导的肺泡上皮细胞凋亡及炎症反应的抑制

          作用
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                          2 #
          林 海 ,易金容 ,饶运帷(1.赣南医学院第一附属医院呼吸与危重医学科,江西 赣州 341000;2.赣州市
                                    1
                 1*
          妇幼保健院麻醉科,江西 赣州 341000)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)22-2721-06
          DOI  10.6039/j.issn.1001-0408.2023.22.06


          摘  要  目的  基于磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路,探讨芒柄花素对脂多糖(LPS)诱导的肺泡上皮细胞凋亡
          及炎症反应的抑制作用。方法  体外培养肺癌人肺泡基底上皮细胞A549,分为对照组(不干预)、模型组(1 μg/mL LPS)、芒柄花素
          不同浓度组(1 μg/mL LPS+6.25、12.5、25、50 μmol/L芒柄花素),检测各组细胞培养液中炎症因子(白细胞介素8、肿瘤坏死因子α)
          水平和细胞活力。另取A549细胞分为对照组、模型组(1 μg/mL LPS)、LPS+25组(1 μg/mL LPS+25 μmol/L芒柄花素)、抑制剂组
         (1 μg/mL LPS+20 μmol/L LY294002)、芒柄花素+抑制剂组(1 μg/mL LPS+25 μmol/L 芒柄花素+20 μmol/L LY294002)和芒柄花
          素+激活剂组(1 μg/mL LPS+25 μmol/L芒柄花素+10 μmol/L SC79),检测各组细胞炎症因子分泌水平和mRNA表达水平、细胞凋亡
          情况和PI3K/Akt信号通路关键蛋白表达情况。结果  与模型组比较,25 μmol/L的芒柄花素能显著降低细胞培养液中炎症因子水平,
          显著升高细胞活力(P<0.05)。与对照组比较,模型组细胞中炎症因子的分泌水平和mRNA表达水平,细胞凋亡率,磷酸化Akt、
          磷酸化PI3K蛋白的相对表达量均显著升高(P<0.05);与模型组比较,LPS+25组和抑制剂组细胞上述指标均显著降低(P<0.05);
          与LPS+25组比较,芒柄花素+抑制剂组细胞上述指标均进一步降低,而芒柄花素+激活剂组细胞上述指标则显著升高(P<0.05)。
          结论  芒柄花素能够抑制LPS诱导的肺泡上皮细胞凋亡并改善其炎症反应,上述作用与抑制PI3K/Akt信号通路有关。
          关键词  芒柄花素;肺泡上皮细胞;脂多糖;磷脂酰肌醇3激酶/蛋白激酶B信号通路;凋亡;炎症反应


          Inhibitory  effects  of  formononetin  on  lipopolysaccharide-induced  apoptosis  and  inflammatory  response  in
          alveolar epithelial cells
          LIN Hai ,YI Jinrong ,RAO Yunwei(1.  Dept.  of  Respiratory  and  Critical  Care  Medicine,  the  First  Affiliated
                 1
                            2
                                          1
          Hospital  of  Gannan  Medical  College,  Jiangxi  Ganzhou  341000,  China;2.  Dept.  of  Anesthesiology,  Ganzhou
          Maternal and Child Health Hospital, Jiangxi Ganzhou 341000, China)

          ABSTRACT   OBJECTIVE  To  investigate  the  inhibitory  effects  of  formononetin  on  lipopolysaccharide (LPS)-induced  apoptosis
          and  inflammatory  response  in  alveolar  epithelial  cells  through  phosphoinositide  3-kinase (PI3K)/protein  kinase  B (Akt)  signaling
          pathway. METHODS  Human lung cancer alveolar basal epithelial cells A549 were cultured in vitro and divided into control group
         (no intervention), model group (1 μg/mL LPS), different concentrations of formononetin groups (1 μg/mL LPS+6.25, 12.5, 25,
          50  μmol/L  formononetin).  The  levels  of  inflammatory  factors (interleukin-8,  tumor  necrosis  factor- α)  and  cell  viability  were
          detected  in  each  group. Another A549  cells  were  divided  into  control  group,  model  group (1  μg/mL  LPS),  LPS+25  group (1  μg/mL
          LPS+25  μmol/L  formononetin),  inhibitor  group (1  μg/mL  LPS+20  μmol/L  LY294002),  formononetin+inhibitor  group (1  μg/mL
          LPS+25 μmol/L formononetin+20 μmol/L LY294002) and formononetin+activator group (1 μg/mL LPS+25 μmol/L formononetin+
          10 μmol/L SC79). The secretion levels and mRNA expressions of inflammatory factors, cell apoptosis, and expressions of the key
          proteins  of  PI3K/Akt  signaling  pathway  were  detected  in  each  group.  RESULTS  Compared  with  model  group,  the  levels  of
          inflammatory  factors  were  decreased  significantly  after  the  intervention  of  25  μmol/L  of  formononetin,  and  the  cell  viability  was
          increased  significantly (P<0.05).  Compared  with  the  control  group,  the  secretion  levels  and  mRNA  expressions  of  inflammatory
                                                             factors,  apoptotic  rate,  and  relative  expressions  of
             Δ 基金项目 江西省省级科技计划项目(No.20192BAB205009);
          江西省卫生健康委科技计划项目(No.202130701)                       phosphorylated  Akt  and  phosphorylated  PI3K  of  the  model
             *第一作者 主治医师,硕士。研究方向:呼吸感染及呼吸危重症。
                                                             group  were  increased  significantly (P<0.05).  Compared  with
          E-mail:xinyulinhai@163.com
                                                             the  model  group,  the  above  indexes  of  the  LPS+25  group  and
             # 通信作者 主治医师,硕士。研究方向:围手术期重要脏器保护、
          器官功能损伤机制及防治。E-mail:yijinrong88@126.com             the  inhibitor  group  were  decreased  significantly (P<0.05).


          中国药房  2023年第34卷第22期                                              China Pharmacy  2023 Vol. 34  No. 22    · 2721 ·
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