背景：制备适宜的功能性消化不良小鼠模型能够为后续临床治疗和用药研究提供可靠的动物模型。

目的：运用联合多因素方法造模制备成年小鼠功能性消化不良模型。

方法：60只昆明小鼠随机分为空白对照组和模型组，每组30只。空白对照组小鼠每日灌胃2%蔗糖溶液0.2m L，持续8 d。模型组在经典碘乙酰胺造模方法联合间日给食的基础上，放入水箱中持续游泳20m in，1 h后给予左旋精氨酸溶液5.7 g/kg灌胃，持续5 d，从第6天开始给予冷大黄水煎液2.9 g/kg 灌胃3 d。观察小鼠行为学变化及光镜下病理形态学变化来确定成模效果。实验方案经承德医学院动物实验伦理委员会批准(批准号为CDMULAC--011)。

结果与结论：与对照组相比，模型组小鼠出现了毛发不光、拱背、体质量呈现下降趋势等特征变化，小肠推进率与胃内容物排空率均有下降现象，光镜下观察胃组织、肠组织切片显示有轻度损伤现象；提示在成年小鼠中运用联合多因素造模方法能够成功制备功能性消化不良模型，并且此种方法所制备的动物模型小鼠没有明显坏死、糜烂等器质性病变，说明此种制备成年功能性消化不良小鼠模型的方法可行。

BACKGROUND: A suitable rat model of functional dyspepsia is a reliable animal model for subsequent clinical treatment and drug research.

OBJECTIVE: To prepare a model of functional dyspepsia in adult mice using a combined multi-factor method.

METHODS: Sixty Kunming mice were randomly divided into a blank control group and a model group, with 30 mice in each group. The mice in the blank control group were orally administered 0.2 mL of a 2% sucrose solution for 8 continuous days. Based on the classic iodoacetamide modeling method combined with daily feeding, the model group was subjected to force swimming in a water tank for 20 minutes, and 1 hour later, themice were orally administered 5.7 g/kg L-arginine solution for 5 days, followed by oral administration of cold rhubarb decoction 2.9g/gk for another 3 days. The behavioral and pathological changes under light microscope were observed to determine the modeling effect. The study protocol was approved by the Animal Ethic Committee of Chengde Medical College, No. CDMULAC--011.

RESULTS AND CONCLUSION: Compared with the control group, the model group showed a reduction in hair color, arch back and body mass, and the intestinal propulsion rate and gastric emptying rate both had a downtrend. Intestinal tissue sections showed mild damage under the light microscope. Therefore, the combined multi-factor modeling method used in in the adult mice can successfully prepare the functional dyspepsia model. Moreover, the animal model prepared by this method has no obvious organic lesions, such as necrosis and erosion, indicating that this is a feasible method to prepare the adult mouse model of functional dyspepsia.

0 引言Introduction

功能性消化不良是消化系统中普遍存在的一种慢性胃肠疾病，由于生活节奏的加快导致此病的发病率逐年升高，但是对于其具体的发病机制还尚未清楚，因而成为研究的热点，故为临床研究提供可靠的动物模型至关重要。目前功能性消化不良大鼠动物模型的制备方法均为单因素刺激，可分为经典的碘乙酰胺法(刺激因素为夹尾激怒)与左旋精氨酸法(左旋精氨酸作为造模刺激药物)[1-7]；但是联合多因素制备功能性消化不良小鼠动物模型研究还未深入。联合多因素制备功能性消化不良动物模型尝试在短时间内利用成年小鼠制备功能性消化不良模型，除了可以降低单一药物的自愈性，进一步模拟患者疾病特征的真实情况，也是制备成年小鼠功能性消化不良模型的一次探索，为后续临床治疗和用药研究提供一种动物模型基础。

1 材料和方法 Materials and methods

1.1 设计 随机对照动物实验。

1.2 时间及地点 实验于2019年1至7月在承德医学院基础医学研究所完成。

1.3 材料

1.3.1 实验动物SPF级10周龄，成年昆明种雌性小鼠60只，体质量30-40 g，由辽宁长生生物技术有限公司提供，许可证号：SCXK(辽)2015-0003。

1.3.2 实验药品、试剂及仪器 活性碳粉(批号：，天津欧博凯化工有限公司)；多聚甲醛(批号：，天津市福晨化学试剂厂)；碘乙酰胺(批号：O0920A,美仑生物技术有限公司)；L-精氨酸(批号：F0110A，美仑生物技术有限公司)；大黄饮片(购自北京同仁堂药店)；Shandon Excelsior全自动全封闭组织脱水机(美国Thermo公司)；RM 2125 RT石蜡切片机(德国Leica公司)；TK-218型恒温摊片烤片机(孝感市泰维电子设备有限公司)；BH-2型OLYMPUS显微镜及摄像装置(日本O lym pus公司)。

1.4 实验方法