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贝母素乙对肺炎链球菌诱导肺泡上皮细胞损伤的影响及机制
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          张 睿 ,李翠红 ,王有琴 ,关君艳 [1. 湖北医药学院附属随州医院(随州市中心医院)儿科,湖北 随州
                                            2 #
                                   1
                 1*
          441300;2.湖北文理学院附属襄阳市中心医院儿科,湖北 襄阳 441021]
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2025)07-0820-06
          DOI  10.6039/j.issn.1001-0408.2025.07.09

          摘   要  目的  探究贝母素乙(PEI)调节伏隔核Ras相关的C3肉毒素底物1(Rac1)/蛋白激酶B(Akt)/核因子κB(NF-κB)信号通路
          对肺炎链球菌(SP)诱导肺泡上皮细胞损伤的影响。方法  取人肺泡上皮细胞HPAEpiC,随机分为对照组(Control组),SP组(1×
            8
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          10  cfu/mL的SP菌液),PEI低、中、高浓度组(1×10  cfu/mL的SP菌液+0.05、0.10、0.20 mmol/L的PEI)和PEI高浓度+Akt通路激活
          剂组(1×10  cfu/mL的SP菌液+0.20 mmol/L的PEI+10 μmol/L的SC79)。除Control组外,其余各组细胞均以SP菌液和(或)相应
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          药液处理。24 h后,检测各组细胞上清液中炎症因子(白细胞介素6、18、1β)水平、细胞氧化应激指标[乳酸脱氢酶(LDH)、超氧化
          物歧化酶(SOD)、活性氧(ROS)]含量、凋亡率和增殖/凋亡相关蛋白[周期蛋白依赖性激酶1(CDK1)、B细胞淋巴瘤2相关X蛋白
         (Bax)]、通路相关蛋白(Rac1、Akt及磷酸化Akt、NF-κB及磷酸化NF-κB)的表达情况。结果  与Control组比较,SP组细胞上清液
          中炎症因子水平,LDH、ROS含量,凋亡率,Bax、Rac1蛋白的表达和Akt、NF-κB蛋白的磷酸化水平均显著升高或上调,SOD含量、
          CDK1蛋白的表达均显著降低或下调(P<0.05)。与SP组比较,PEI各浓度组上述指标均显著改善,且呈浓度依赖性(P<0.05);而
          SC79可显著逆转高浓度PEI的改善作用(P<0.05)。结论  PEI可以减轻SP诱导的肺泡上皮细胞炎症和氧化应激损伤,抑制细胞
          凋亡,上述作用可能是通过抑制Rac1/Akt/NF-κB信号通路而实现的。
          关键词  贝母素乙;肺炎链球菌;肺泡上皮细胞;Rac1/Akt/NF-κB信号通路


          Effects  of  peiminine  B  on  Streptococcus  pneumoniae-induced  alveolar  epithelial  cell  injury  and  its
          mechanism
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                     1
          ZHANG Rui ,LI Cuihong ,WANG Youqin ,GUAN Junyan [1.  Dept.  of  Pediatrics,  Suizhou  Hospital Affiliated
                                                1
          to  Hubei  Medical  College (Suizhou  Central  Hospital),  Hubei  Suizhou  441300,  China;2.  Dept.  of  Pediatrics,
          Xiangyang  Central  Hospital  Affiliated  to  Hubei  University  of  Arts  and  Sciences,  Hubei  Xiangyang  441021,
          China]
          ABSTRACT     OBJECTIVE To investigate the effects of peiminine B (PEI) on Streptococcus pneumoniae (SP)-induced alveolar
          epithelial  cell  injury  by  regulating  the  Ras-related  C3  botulinum  toxin  substrate  1  in  nucleus  accumbens (Rac1)/protein  kinase  B
         (Akt)/nuclear  factor  κB (NF- κB)  signaling  pathway.  METHODS  Human  alveolar  epithelial  cells (HPAEpiC)  were  taken  and
          randomly divided into the Control group, SP group (1×10  cfu/mL SP bacterial solution), low-, medium-, and high-concentration
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          PEI  groups (1×10   cfu/mL  SP  bacterial  solution+0.05,  0.10,  0.20  mmol/L  PEI),  and  high-concentration  PEI+Akt  activator  group
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         (P-H+SC79  group,  1×10   cfu/mL  SP  bacterial  solution+0.20  mmol/L  PEI+10  μmol/L  SC79).  Except  for  the  Control  group,  the
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          other groups of cells were treated with SP bacterial solution and/or corresponding drug solution. After 24 h of treatment, the levels
          of  inflammatory  factors (interleukin-6,  -18,  -1β)  in  the  supernatant  solution,  the  contents  of  oxidative  stress  indexes  [lactate
          dehydrogenase (LDH),  reactive  oxygen  species (ROS)  and  superoxide  dismutase (SOD)],  apoptosis  rate,  as  well  as  the
          expressions  of  proliferation/apoptosis-related  proteins  [cyclin-dependent  kinase  1 (CDK1),  B  cell  lymphoma-2  related  X  protein
         (Bax)]  and  pathway-related  proteins (Rac1, Akt,  phosphorylated Akt,  NF-κB  and  phosphorylated  NF-κB)  were  detected  in  each
          group.  RESULTS  Compared  with  the  Control  group,  the  levels  of  inflammatory  factors  in  supernatant  solution,  LDH  and  ROS
                                                              contents,  apoptosis  rate,  the  protein  expressions  of  Bax  and
              Δ 基金项目 湖 北 省 卫 生 健 康 委 科 研 立 项 项 目(No. WJ2019-   Rac1  and  the  phosphorylation  levels  of Akt  and  NF-κB  in  the
          AB008)                                              SP  group  were  significantly  increased  or  up-regulated,  while
             *第一作者 主治医师,硕士。研究方向:儿科呼吸疾病的基础与
                                                              SOD  content  and  the  protein  expression  of  CDK1  were
          临床。E-mail:ziguym@163.com
              # 通信作者 副主任医师,硕士。研究方向:儿科呼吸疾病的基础                  significantly   decreased   or   down-regulated  (P<0.05).
          与临床。E-mail:xwqdc83@163.com                          Compared with the SP group, the above indexes in PEI groups


          · 820 ·    China Pharmacy  2025 Vol. 36  No. 7                               中国药房  2025年第36卷第7期
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