首页|期刊导航|中国实验动物学报|复合因素诱导轻至中度慢性萎缩性胃炎模型的建立与验证

复合因素诱导轻至中度慢性萎缩性胃炎模型的建立与验证OA

Establishment and validation of a model of mild-to-moderate chronic atrophic gastritis induced by compound factors

中文摘要英文摘要

目的 建立复合因素诱导的轻至中度慢性萎缩性胃炎(chronic atrophic gastritis,CAG)大鼠模型,并评估验证其在药效实验中的应用.方法 采用1-甲基-3-硝基-1-亚硝基胍(1-methyl-3-nitro-1-nitrosoguanidine,MNNG)联合雷尼替丁和饥饱失常三种因素复合诱导建立CAG大鼠模型,于造模14~24周不同节点每次分别剖检空白组和造模组3只大鼠,以进行胃组织病理学检查判断模型进展.于造模成熟节点选取20只空白大鼠入正常对照组,选取40只造模大鼠随机均衡分为模型组和叶酸组,分组后对各组动物进行灌胃给药,每天一次,共计28 d.实验期间监测各组存活动物体质量和摄食量,给药14和28 d分别剖杀各组半数动物进行胃组织病理学检查.结果 与空白组相比,造模组大鼠造模35 d起体质量明显降低,在造模46 d起摄食量亦显著降低,造模23周动物胃体和胃窦固有腺体轻度-中度变性/坏死,腺上皮细胞轻度丢失,胃体轻度炎细胞浸润,于24周维持稳定.与正常组比,模型组大鼠给药期间体质量和摄食量均显著降低,与模型组比,叶酸组大鼠给药第18天起体质量显著升高,给药第15天起摄食量显著升高,给药28 d后胃体萎缩评分和胃损伤评分均显著降低,胃体固有腺体萎缩发生率减少,萎缩程度减轻.结论 三种因素复合法造模24周后可诱导出稳定的轻至中度CAG大鼠模型,适用于药物药效作用的评价.

Objective To establish a rat model of mild-to-moderate chronic atrophic gastritis(CAG)induced by multiple factors and to evaluate and validate its application in pharmacodynamic testing.Methods A rat CAG model was established by inducing three composite factors:1-methyl-3-nitro-1-nitrosoguanidine(MNNG)combined with ranitidine and feeding disorders.From 14 to 24 weeks post-modeling,three rats each from the blank and model groups were dissected at each time point to conduct gastric tissue pathological examination to assess model progression.At the mature node of model creation,20 normal rats were selected for the control group,and 40 model rats were randomly and evenly divided into model and folic acid groups.The animals in each group were administered by gavage once daily for 28 d.Body mass and food intake in each group were monitored,and half of the animals in each group were euthanized for gastric tissue pathology examination on days 14 and 28 of treatment.Results Compared with the blank group,model rats showed a significant decrease in body mass starting from day 35 of modeling,and a significant decrease in food intake starting from day 46.After 23 weeks,there was mild to moderate degeneration/necrosis of the mucosal glands in the gastric body and antrum,slight loss of glandular epithelial cells,and mild infiltration of inflammatory cells in the gastric body,which remained stable by week 24.Compared with the model group,the folic acid group showed a significant increase in body mass starting from day 18 of administration,and a significant increase in food intake starting from day 15;gastric atrophy and gastric injury scores were significantly reduced after 28 d of administration,as was the incidence and degree of gastric proper gland atrophy.Conclusions The three-compound factor modeling method induced a stable mild-to-moderate rat CAG model in 24 weeks,which is suitable for drug efficacy evaluation.

张文强;马丽清;张发福;黄雪映;唐瑞欣;杨威;郭健敏

广州湾区生物医药研究院,广东莱恩医药研究院有限公司,广东省药物非临床评价与研究重点实验室,国家中药现代化工程技术研究中心中药非临床评价分中心,广东省眼科药物创制与评价工程技术研究中心,广州 510990广州湾区生物医药研究院,广东莱恩医药研究院有限公司,广东省药物非临床评价与研究重点实验室,国家中药现代化工程技术研究中心中药非临床评价分中心,广东省眼科药物创制与评价工程技术研究中心,广州 510990广州湾区生物医药研究院,广东莱恩医药研究院有限公司,广东省药物非临床评价与研究重点实验室,国家中药现代化工程技术研究中心中药非临床评价分中心,广东省眼科药物创制与评价工程技术研究中心,广州 510990广州湾区生物医药研究院,广东莱恩医药研究院有限公司,广东省药物非临床评价与研究重点实验室,国家中药现代化工程技术研究中心中药非临床评价分中心,广东省眼科药物创制与评价工程技术研究中心,广州 510990广州湾区生物医药研究院,广东莱恩医药研究院有限公司,广东省药物非临床评价与研究重点实验室,国家中药现代化工程技术研究中心中药非临床评价分中心,广东省眼科药物创制与评价工程技术研究中心,广州 510990广州湾区生物医药研究院,广东莱恩医药研究院有限公司,广东省药物非临床评价与研究重点实验室,国家中药现代化工程技术研究中心中药非临床评价分中心,广东省眼科药物创制与评价工程技术研究中心,广州 510990广州湾区生物医药研究院,广东莱恩医药研究院有限公司,广东省药物非临床评价与研究重点实验室,国家中药现代化工程技术研究中心中药非临床评价分中心,广东省眼科药物创制与评价工程技术研究中心,广州 510990

生物科学

慢性萎缩性胃炎大鼠模型MNNG胃组织病理学检查叶酸

chronic atrophic gastritisrat modelMNNGgastric tissue pathological examinationfolic acid

《中国实验动物学报》 2026 (5)

710-718,9

广东省药物非临床评价与研究重点实验室(2024),国家科技创业领军人才(SQ2024RA3E000198).Funded by Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and Research(2024),National Leading Talent in Technology Entrepreneurship(SQ2024RA3E000198).

10.3969/j.issn.1005-4847.2026.05.008

评论