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甘草甜素对大鼠幽门螺杆菌相关性胃炎的改善作用及机制
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          刘誉华 ,刘 莲 ,汪九重 ,黄 丹 ,周素芳 ,肖欢智 ,安祯祥 (1.贵州中医药大学第一临床医学院,贵阳
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          550001;2.贵州医科大学临床微生物与免疫学教研室,贵阳 550001;3.中国中医科学院广安门医院传染病科,
          北京 100053;4.贵州中医药大学第一附属医院脾胃病科,贵阳 550001)
          中图分类号  R965;R285.5      文献标志码  A      文章编号  1001-0408(2024)02-0166-06
          DOI  10.6039/j.issn.1001-0408.2024.02.08

          摘   要  目的  探讨甘草甜素(GL)对大鼠幽门螺杆菌(HP)相关性胃炎的改善作用及机制。方法  以接种1×10  cfu/mL HP建立
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          HP 相关性胃炎大鼠模型,将造模成功大鼠随机分为模型组、阳性对照组(HP 标准四联方案)和 GL 低、中、高剂量组(5、20、50
          mg/kg),每组12只;另取12只正常大鼠作为正常对照组。除正常对照组和模型组大鼠灌胃等体积生理盐水外,其他各组大鼠灌胃
          相应药物,每天1次,连续30 d。给药结束后大鼠行 C尿素呼气试验,记录超基准值(DOB);观察大鼠胃黏膜组织病理变化和细胞
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          形态学变化,并进行病理评分;检测大鼠胃黏膜组织中白细胞介素8(IL-8)、IL-1β、肿瘤坏死因子α(TNF-α)、活性氧(ROS)、丙二
          醛(MDA)水平,高迁移率族蛋白B1(HMGB1)、核因子κB(NF-κB)mRNA相对表达量,一氧化氮合酶(iNOS)、HMGB1蛋白相对
          表达量以及 NF-κB p65 磷酸化水平。结果  与正常对照组比较,模型组大鼠 DOB 值,胃黏膜组织病理评分,IL-8、IL-1β、TNF-α、
          ROS、MDA水平,HMGB1、NF-κB mRNA相对表达量,iNOS、HMGB1蛋白相对表达量和NF-κB p65磷酸化水平均显著升高(P<
          0.05);大鼠胃黏膜上皮细胞结构不完整且数量减少,细胞碎片及空泡增多,细胞固缩明显。与模型组比较,GL各剂量组和阳性对
          照组上述指标变化均显著逆转(P<0.05),且GL高剂量组上述指标变化均较GL低、中剂量组更显著(P<0.05);大鼠胃黏膜细胞
          病理变化均改善。结论  GL可能通过抑制HMGB1/NF-κB信号通路的激活,抑制炎症和氧化应激反应,从而减轻HP引起的胃黏
          膜损伤。
          关键词  甘草甜素;高迁移率族蛋白B1;核因子κB;幽门螺杆菌相关性胃炎;胃黏膜损伤

          Improvement effects of glycyrrhizin on Helicobacter pylori-associated gastritis in rats and its mechanism
          LIU Yuhua ,LIU Lian ,WANG Jiuchong ,HUANG Dan ,ZHOU Sufang ,XIAO Huanzhi ,AN Zhenxiang             4
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         (1.  The  First  Clinical  Medical  College  of  Guizhou  University  of  Traditional  Chinese  Medicine,  Guiyang
          550001,  China;2. Teaching  and  Research  Section  of  Clinical  Microbiology  and  Immunology,  Guizhou  Medical
          University,  Guiyang  550001,  China;3.  Dept.  of  Infectious  Diseases,  Guang’anmen  Hospital,  China Academy
          of Chinese Medical Sciences, Beijing 100053, China;4. Dept. of Gastroenterology, the First Affiliated Hospital
          of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China)

          ABSTRACT    OBJECTIVE  To  investigate  the  improvement  effects  of  glycyrrhizin (GL)  on  Helicobacter  pylori (HP)-associated
          gastritis  in  rats  and  its  mechanism.  METHODS  HP-associated  gastritis  rat  model  was  induced  by  inoculating  with  1×10   cfu/mL
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          HP. The model rats were randomly divided into model group, positive control group (HP standard quadruple group), GL low-dose,
          medium-dose  and  high-dose  groups (5,  20,  50  mg/kg),  with  12  rats  in  each  group.  Another  12  healthy  rats  were  selected  as
          normal  control  group.  Except  the  normal  control  group  and  model  group  were  given  constant  volume  of  normal  saline
          intragastrically,  the  other  groups  were  given  corresponding  drugs  intragastrically,  once  a  day,  for  30  consecutive  days.  After
          administration,  rats  received  C  urea  breath  test,  and  delta-over-baseline (DOB)  was  recorded;  the  pathological  and  cellular
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          morphological changes of gastric mucosa in rats were observed, and pathological scoring was performed; the levels of interleukin-8
                                                             (IL-8),  IL-1β,  tumor  necrosis  factor- α (TNF- α),  reactive
              Δ 基金项目 贵州省科技计划项目(No. 黔科合支撑〔2020〕4Y077
                                                              oxygen  species (ROS)  and  malondialdehyde (MDA)  were
          号);贵州省卫生健康委科学技术基金项目(No.gzwkj2023-139);贵州
          中医药大学国家与省级科技创新人才团队培育项目(No.贵中医TD合                    detected  in  gastric  mucosa  of  rats;  mRNA  expressions  of  high
          字〔2022〕005号)                                        mobility  group  box-1  protein (HMGB1)  and  nuclear  factor-
             *第一作者 副主任医师,博士研究生。研究方向:中医药防治脾
                                                              κ -B (NF- κB),  relative  expressions  of  nitric  oxide  synthases
          胃病。电话:0851-85636327。E-mail:394717866@qq.com
                                                             (iNOS)  and  HMGB1,  the  phosphorylation  level  of  NF- κB
              # 通信作者 主任医师,博士生导师,博士。研究方向:中医药防治
          脾胃病、肝病。电话:0851-85636327。E-mail:407206115@qq.com     p65  were  also  detected  in  rats.  RESULTS  Compared  with


          · 166 ·    China Pharmacy  2024 Vol. 35  No. 2                               中国药房  2024年第35卷第2期
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