18β-甘草次酸对K19-C2mE转基因鼠胃肿瘤的抑制作用及其机制

目的: 探讨18β-甘草次酸(18β-GA)对K19-C2mE转基因鼠胃肿瘤的抑制作用,阐明其抑制炎症反应及肿瘤生成的作用机制。方法: 采用K19-C2mE自发胃肿瘤转基因鼠模型,随机分为对照组(n=36)和实验组(n=34),对照组小鼠正常饮水,实验组小鼠给予质量浓度0.1%的18β-GA饮水投药。52周后处死小鼠取胃组织,分别观察和测量胃肿瘤形态和大小;HE染色观察小鼠胃组织病理学形态;免疫组织化学染色及H-score评分检测对照组和实验组肿瘤组织炎症因子环氧化酶2(COX-2)和白细胞介素1β(IL-1β)表达水平。结果: 2组小鼠体质量随周龄变化无明显差异。对照组和实验组小鼠胃肿瘤发生率分别为77.8%(28/36)和41.2%(14/34),实验组肿瘤发生率显著降低(P=0.002);与对照组比较,实验组小鼠胃黏膜肉眼形态较规则,胃部肿块体积小,表面光滑,黏膜充血及溃疡少见;HE染色显微镜下观察,实验组炎症反应较轻,细胞及组织结构异型性反应减弱;免疫组织化学染色及H-score评分,与对照组比较,实验组小鼠胃组织中COX-2和IL-1β表达水平明显降低(P<0.001)。结论: 18β-GA能够显著降低K19-C2mE转基因鼠胃肿瘤的发生率,有效减轻胃黏膜炎症反应,其机制可能是通过下调胃黏膜炎症因子COX-2和IL-1β表达水平从而抑制胃肿瘤的发生发展。

Inhibitory effect of 18β-glycyrrhetinic acid on gastric tumor in K19-C2mE transgenic mice and its mechanisms

Objective: To investigate the inhibitory effect of 18β-glycyrrhetinic acid (18β-GA) on the occurrence and development of gastric tumor in the K19-C2mE transgenic mice, and to elucidate the inhibition mechanisms of 18β-GA on inflammation and tumorigenesis.Methods: K19-C2mE transgenic mice with gastric tumor were randomly divided into control group (n=36) and experimental group (n=34).The mice in experimental group were given the water with 0.1%18β-GA, while the mice in control group were given normal water.All animals were sacrificed at 52 weeks, the morphology and size of tumors were observed and measured respectively; the pathomorphology of stomach tissue was observed by hematoxylin and eosin (HE) staining; immunohistochemistry method and the H-score were used to detect the expression levels of cyclooxygenase-2 (COX-2) and interleukin-1β (IL-1β) in stomach tissue.Results: The incidence of gastric tumor in experimental group was significantly decreased compared with control group (41.18% vs 77.78%, P=0.002).The morphology of gastric mucosa was regular in experimental group, the size of gastric tumor was smaller, and the surface of tissue was more smooth compared with control group;little hyperemia and ulcer were observed.The response of inflammation was mild in experimental group, and there were little atypia in cellular morphology and organizational structure.Compared with control group, the expression levels of COX-2 and IL-1β in stomach tissue of the mice in experimental group were decreased (P<0.001).Conclusion: 18β-GA could reduce the incidence of gastric tumor in the K19-C2mE transgenic mice.18β-GA may inhibit the occurrence and development of gastric tumor by regulating the expression levels of COX-2 and IL-1β.