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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。
OBJECTIVE: To investigate the inhibitory effect of 18β-GA on gastric neoplasia in K19-C2mE transgenic mice and to elucidate its mechanism of inhibiting inflammatory reaction and tumorigenesis. Methods: The mice were randomly divided into control group (n = 36) and experimental group (n = 34). The mice in the control group received normal drinking water. The mice in the experimental group were given 0.1% 18β -GA water dosing. After 52 weeks, the mice were sacrificed and the gastric tissues were sacrificed. Morphology and size of gastric tumors were observed and measured respectively. The histopathological changes of gastric tissues were observed by HE staining. Immunohistochemical staining and H-score were used to detect the expression of inflammatory cytokines Cyclooxygenase 2 (COX-2) and interleukin 1β (IL-1β) expression levels. Results: There was no significant difference in the body weight of the two groups with the change of the age. The incidence of gastric tumors was 77.8% (28/36) and 41.2% (14/34) in the control group and the experimental group, respectively. The incidence of tumor in the experimental group was significantly decreased (P = 0.002). Compared with the control group, the experimental group The morphology of gastric mucosa of rats was relatively regular, the volume of gastric mass was small, the surface was smooth, mucosal hyperemia and ulcer were rare. Under the microscope of HE staining, the inflammatory reaction in the experimental group was lighter and the atypical reaction of cells and tissue structure was weakened. Immunohistochemical staining and Compared with the control group, the expression levels of COX-2 and IL-1β in gastric mucosa of experimental mice were significantly decreased (P <0.001) by H-score. Conclusion: 18β-GA can significantly reduce the incidence of gastric neoplasia in K19-C2mE transgenic mice and effectively reduce the gastric mucosal inflammatory response. The possible mechanism is that 18β-GA can inhibit the expression of COX-2 and IL-1β in gastric mucosa Development took place.