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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