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

作　　者：赵丹[1] 曹东慧[1] 金美善[2] 吴孟辉 王玥琦 杨娜[1] 周天宇[3] 张厚君 姜晶[1] 曹雪源[3] ZHAO Dan;CAO Donghui;JIN Meishan;WU Menghui;WANG Yueqi;YANG Na;ZHOU Tianyu;ZHANG Houjun;JIANG Jing;CAO Xueyuan(Department of Clinical Research,First Hospital,Jilin University,Changchun 130021,China;Center of Pathological Diagnosis,First Hospital,Jilin University,Changchun 130021,China;Department of Gastric and Colorectal Surgery,First Hospital,Jilin University,Changchun 130021,China)

机构地区：[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

出　　处：《吉林大学学报（医学版）》2018年第6期1150-1155,共6页Journal of Jilin University：Medicine Edition

基　　金：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)

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。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.

关 键 词：18Β-甘草次酸 慢性胃炎 胃肿瘤 转基因小鼠 细胞分化 

分 类 号：R735.2[医药卫生—肿瘤]