β-甘草次酸对炎症相关胃癌的抑制作用及其机制

doi:10.13481/j.1671-587x.20180607

吉林大学学报(医学版) ›› 2018, Vol. 44 ›› Issue (06): 1150-1155.doi: 10.13481/j.1671-587x.20180607

β-甘草次酸对炎症相关胃癌的抑制作用及其机制

赵丹¹, 曹东慧¹, 金美善², 吴孟辉³, 王玥琦¹, 杨娜¹, 周天宇³, 张厚君³, 姜晶¹, 曹雪源³

1. 吉林大学第一医院临床研究部, 吉林长春 130021;
2. 吉林大学第一医院病理诊断中心, 吉林长春 130021;
3. 吉林大学第一医院胃结直肠外科, 吉林长春 130021

收稿日期:2018-02-06 出版日期:2018-11-28 发布日期:2018-11-28
通讯作者: 曹雪源,教授,硕士研究生导师(Tel:0431-88785602,Email:caoxy@aliyun.com) E-mail:caoxy@aliyun.com
作者简介:赵丹(1994-),女,内蒙古自治区呼伦贝尔市人,在读医学硕士,主要从事肿瘤分子流行病学和消化道肿瘤的化学预防方面的研究。
基金资助:
国家自然科学基金资助课题（81673145）；吉林省科技厅科技引导计划国际科技合作项目资助课题（20180414055GH）

Inhibitory effect of 18β-glycyrrhetinic acid on inflammation-related gastric cancer and its mechanism

ZHAO Dan¹, CAO Donghui¹, JIN Meishan², WU Menghui³, WANG Yueqi¹, YANG Na¹, ZHOU Tianyu³, ZHANG Houjun³, JIANG Jing¹, CAO Xueyuan³

1. Department of Clinical Research, First Hospital, Jilin University, Changchun 130021, China;
2. Center of Pathological Diagnosis, First Hospital, Jilin University, Changchun 130021, China;
3. Department of Gastric and Colorectal Surgery, First Hospital, Jilin University, Changchun 130021, China

Received:2018-02-06 Online:2018-11-28 Published:2018-11-28

摘要/Abstract

摘要： 目的：探讨18β-甘草次酸（18β-GA）对炎症相关胃癌的抑制作用，并阐明其作用机制。方法：将72只K19-Wnt/C2mE转基因胃癌小鼠随机分为18β-GA给药组（n=36）和对照组（n=36）。18β-GA给药组小鼠给予质量浓度0.1% 18β-GA饮水，对照组小鼠正常饮水。52周后观察2组小鼠胃癌发生率和胃黏膜形态表现，采用免疫组织化学染色法检测2组小鼠胃黏膜上皮细胞中Ki-67、F4/80、ATP4a、KCNE2、胃蛋白酶原C （PGC）、Wnt-1、β-catenin和环氧化酶2（COX-2）的组织化学评分（H-score）。结果：对照组小鼠胃黏膜出现隆起型肿瘤、不典型增生和慢性胃炎。与对照组比较，18β-GA给药组小鼠胃癌发生率明显降低（P=0.019），肿瘤体积明显缩小（P<0.01），胃黏膜细胞及组织结构异型性减少，炎症反应减轻。与对照组比较，18β-GA给药组小鼠胃黏膜上皮细胞中Ki-67、F4/80、Wnt-1、β-catenin和COX-2的H-score明显降低（P<0.05），ATP4a、KCNE2和PGC H-score明显升高（P<0.05）。结论：18β-GA可抑制K19-Wnt/C2mE转基因小鼠胃癌的发生，其作用机制可能是18β-GA减轻胃黏膜内炎症反应，有效改善胃黏膜上皮细胞分化，从而抑制胃癌发病。

关键词: 18β-甘草次酸, 慢性胃炎, 胃肿瘤, 转基因小鼠, 细胞分化

Abstract: Objective: To explore the inhibitory effect of 18β-glycyrrhetinic acid (18β-GA) on the inflammation-related gastric cancer, and to clarify its mechanism.Methods: A total of 72 K19-Wnt/C2mE transgenic mice with gastric cancer were randomly divided into 18β-GA treatment group (drinking water contain 0.1% 18β-GA, n=36) and control group (drinking normal water, n=36). After 52 weeks, the incidence of gastric cancer and morphology of gastric mucosa of the mice in two groups were detected. Immunohistochemistry staining was used to detect the histochemistry scores(H-score) of Ki-67, F4/80, ATP4a, KCNE2, pepsinogen C (PGC), Wnt-1, β-catenin, and cyclooxygenase-2 (COX-2) in gastric mucosa epithelial cells of the mice in two groups.Results: The gastric mucosa of the mice in control group showed protruded lesions, atypical hyperplasia and chronic gastritis. Compared with control group,the incidence(P=0.019) and the volume of gastric cancer of the mice in 18β-GA treatment group were significantly decreased (P<0.01);the structural heterozygosities of gastric cells and tissue were decreased,and the inflammation reactions of the mice in 18β-GA treatment group were alleviated. Compared with control group, the H-scores of Ki-67, F4/80, Wnt-1, β-catenin, and COX-2 in gastric mucosa epithelial cells of the mice in 18β-GA treatment group were decreased (P<0.05), and the H-scores of ATP4a, KCNE2,and PGC were increased (P<0.05).Conclusion: 18β-GA can significantly inhibit the occurrence of gastric cancer in the K19-Wnt/C2mE transgenic mice. The inhibitory effect may be related to alleviating the inflammation reaction and promoting the differentiation of gastric mucosa epithelial cells and inhibiting the occurrence of gastric cancer.

Key words: 18β-glycyrrhetinic acid, chronic gastritis, stomach neoplasms, transgenic mice, cell differentiation

中图分类号:

R735.2

赵丹, 曹东慧, 金美善, 吴孟辉, 王玥琦, 杨娜, 周天宇, 张厚君, 姜晶, 曹雪源. β-甘草次酸对炎症相关胃癌的抑制作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(06): 1150-1155.

ZHAO Dan, CAO Donghui, JIN Meishan, WU Menghui, WANG Yueqi, YANG Na, ZHOU Tianyu, ZHANG Houjun, JIANG Jing, CAO Xueyuan. Inhibitory effect of 18β-glycyrrhetinic acid on inflammation-related gastric cancer and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2018, 44(06): 1150-1155.

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β-甘草次酸对炎症相关胃癌的抑制作用及其机制

Inhibitory effect of 18β-glycyrrhetinic acid on inflammation-related gastric cancer and its mechanism

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