中国中西医结合消化杂志2024,Vol.32Issue(5) :401-407.DOI:10.3969/j.issn.1671-038X.2024.05.06

N-甲基-N-亚硝基脲联合幽门螺杆菌造模致小鼠"炎-癌"转化的研究

The study of N-methyl-N-nitrosourea combined with Helicobacter pylori infection inducing gastric inflammation-cancer transformation process in mice

李俊怡 罗柳茹 张伟健 徐建区 曾晓会 许艺飞 洪欣欣 郭绍举
中国中西医结合消化杂志2024,Vol.32Issue(5) :401-407.DOI:10.3969/j.issn.1671-038X.2024.05.06

N-甲基-N-亚硝基脲联合幽门螺杆菌造模致小鼠"炎-癌"转化的研究

The study of N-methyl-N-nitrosourea combined with Helicobacter pylori infection inducing gastric inflammation-cancer transformation process in mice

李俊怡 1罗柳茹 2张伟健 2徐建区 2曾晓会 3许艺飞 2洪欣欣 2郭绍举2
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作者信息

  • 1. 深圳市中医院脾胃研究所广州中医药大学第四临床医学院(广东深圳,518033);广州中医药大学第五临床医学院
  • 2. 深圳市中医院脾胃研究所广州中医药大学第四临床医学院(广东深圳,518033)
  • 3. 广州中医药大学第五临床医学院
  • 折叠

摘要

目的:探讨N-甲基-N-亚硝基脲(MNU)联合幽门螺杆菌(Hp)在C57BL/6J小鼠胃黏膜"炎-癌"转化进程中的作用.方法:将112只C57BL/6J小鼠分为对照组(3、6、9、12个月,n=8)和模型组(3、6、9、12个月,n=20),模型组小鼠使用MNU灌胃联合Hp感染法造模,2组小鼠分别在3、6、9、12个月时进行取材,观察胃黏膜的肿瘤成瘤情况及该造模方式对胃炎症因子转录水平的影响.结果:MNU联合Hp造模9个月组和12个月组的成瘤率分别约为30%和40%,在造模后的9个月和12个月,胃黏膜可见大量炎性细胞浸润,主要为淋巴细胞和嗜酸粒细胞,并伴有胃黏膜异型增生改变.肿瘤坏死因子(TNF-α)mRNA水平在感染后6、9、12个月均显著上调.白介素-1β(IL-1β)mRNA在造模后3、6个月均显著上调,并在12个月出现显著下调.此外,IL-33的mRNA水平上调不明显,在12个月模型组中IL-33水平显著下调.结论:MNU联合Hp造模显示出明显的炎症浸润表现,在9个月组和12个月组的成瘤率分别约为30%和40%.联合造模可加速C57BL/6J小鼠胃黏膜慢性胃炎至异型增生的病理改变的进程.

Abstract

Objective:To investigate the role of N-methyl-N-nitrosourea(MNU)combined with Helicobacter pylori(Hp)in the"inflammation-cancer"transformation process of gastric mucosa in C57BL/6J mice.Methods:A total of 112 C57BL/6J mice were divided into a control group(3,6,9,12 months,n=8)and a model group(3,6,9,12 months,n=20).Mice in the model group were molded by MNU combined with Hp infection.Tissues were collected from the mice in the modeling group at 3,6,9,and 12 months respectively,to observe tumor for-mation in gastric mucosa and the impact of this modeling method on the transcription levels of gastric inflamma-tion factors.Results:The tumor formation rates in the 9-month and 12-month groups of MNU combined with Hp modeling were approximately 30%and 40%,respectively.After modeling for 9 and 12 months,extensive infil-tration of inflammatory cells,mainly lymphocytes and eosinophils,was observed in the gastric mucosa,accompa-nied by dysplastic changes.The mRNA levels of TNF-α showed a significant upregulation in the 6,9,and 12-month groups after infection.IL-1β was significantly upregulated in the 3,and 6-month groups and declined in the 12-month group.The expression of IL-33,associated with precancerous lesions of gastric cancer,did not show significant upregulation in this study but was significantly downregulated in the 12-month model group.Conclu-sion:MNU combined with Hp modeling showed significant manifestations of inflammation infiltration,with tumor formation rates of approximately 30%and 40%in the 9-month and 12-month groups,respectively.This combined modeling can accelerate the pathological changes from chronic gastritis to dysplasia in C57BL/6J mouse gastric mucosa.

关键词

幽门螺杆菌/N-甲基-N-亚硝基脲/"炎-癌"转化/解痉多肽表达化生/异型增生

Key words

Helicobacter pylori/N-methyl-N-nitrosourea/inflammation-cancer transformation/spasmolytic polypeptide-expressing metaplasia/dysplasia

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基金项目

国家自然科学基金(82374348)

国家自然科学基金(82305133)

国家自然科学基金(82204734)

中国博士后科学基金(2023M732383)

深圳市科技计划(JCYJ20230807094805012)

深圳市医疗卫生三名工程项目(SZZYSM202211002)

出版年

2024
中国中西医结合消化杂志
华中科技大学同济医学院,中国中西医结合学会消化系统疾病专业委员会,中华中医药学会脾胃病专业委员会

中国中西医结合消化杂志

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影响因子:1.363
ISSN:1671-038X
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