Research Progress on Animal Models of Gastric Ulcer of Spleen-Stomach Deficiency Cold Type

doi:10.12300/j.issn.1674-5817.2025.015

Abstract

Abstract:

Gastric ulcer (GU) is one of the common, frequently-occurring and intractable diseases of the digestive system. Spleen-stomach deficiency cold type is the most common and hard-to-cure syndrome pattern of GU, and is both a focus and a challenge in medical research. Therefore, constructing a scientific, reasonable, and clinically practical animal model of GU with spleen-stomach deficiency cold type and formulating objective and effective evaluation criteria are of great significance for in-depth research on the pathogenesis and treatment of GU. In this paper, the methods for constructing GU animal models of spleen-stomach deficiency cold type are comprehensively introduced by systematically reviewing the relevant literature. Firstly, the construction methods of pathological models of GU in Western medicine are introduced, including pyloric ligation method, water immersion-restraint stress method, ethanol-induced method, acetic acid-induced method, etc. This paper expounds the establishment methods for spleen-stomach deficiency cold syndrome type model in traditional Chinese medicine (TCM), including diet disorder method, bitter cold diarrhea method, excessive fatigue method, Qi consumption and Qi impairment method, and overeating sour-flavor method. This paper focuses on the construction methods for disease-syndrome combination GU models of spleen-stomach deficiency cold type, including two-factor modeling method and three-factor modeling method. Meanwhile, the evaluation indices of GU animal models of spleen-stomach deficiency cold type were summarized from various aspects, including animal physical signs ( appearance symptoms, animal behavior, and metabolic indices), as well as tissue morphology and molecular biology-related indicators ( gastric function, oxidative stress, inflammatory factors, other cytokines, four coagulation parameters, intestinal flora detection ), for constructing a comprehensive evaluation system. From the perspective of prescription-based verification, this paper further analyzes the drug composition and pharmacological effects to infer the syndrome type of the treated animal model, so as to verify whether the target animal model is successfully constructed. This review aims to provide a valuable reference for establishing a syndrome-specific GU animal model that closely aligns with clinical reality and embodies the principles of Chinese medicine. This will further advance research on TCM-pattern GU syndromes and deepen the exploration of herbal medicine-based treatments for GU, ultimately promoting the clinical integration and advancement of Chinese medicine in GU therapy.

Key words: Gastric ulcer, Spleen-stomach deficiency cold, Disease-syndrome combination, Animal model

CLC Number:

R-332

LIU Ziqi,LI Yunying,LI Qin,et al. Research Progress on Animal Models of Gastric Ulcer of Spleen-Stomach Deficiency Cold Type[J]. Laboratory Animal and Comparative Medicine, 2025, 45(5): 574-585. DOI: 10.12300/j.issn.1674-5817.2025.015.

Figures/Tables 5

References 56

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方法 Methods	优点 Advantages	缺点 Disadvantages	适用范围 Range of application	病理 Pathology
幽门结扎法 Pyloric ligation method	GU重复性好，实验结果稳定；实验造成的GU部位明确，溃疡程度可控	人为结扎为非生理性GU；实验操作技术要求高	急性GU研究；用于抗GU药物评估；GU相关机制研究	通过胃酸堆积、压迫血管，模拟GU
水浸-束缚应激法 Water immersion-restraint stress method	GU复制率高，重复性好；实验操作简单；能较好模拟应激引发的GU	操作过程缺乏量化标准；可能引发其他生理变化；个体差异影响较大；仅适用于短期研究	应激性GU研究；用于抗应激性GU药物评估；应激反应机制研究	通过束缚、水浸，模拟情志失调模型
乙醇诱导法 Ethanol-induced method	操作方法简单，重复性好，成模效果好；能短时间诱导胃黏膜损伤；GU溃疡程度可控	直接损伤胃黏膜为非生理性溃疡；不适用于长期慢性GU研究；死亡率较高	急性GU研究；用于抗GU、胃黏膜保护药物评估；胃黏膜屏障功能机制研究	通过乙醇灌胃，模拟寒邪或热邪侵袭
乙酸诱导法 Acetic acid-induced method	GU形成后持续时间长，重复性好；造模方法简单；溃疡程度可控	直接损伤胃黏膜为非生理性溃疡；诱导GU局限于慢性GU	慢性GU研究；用于促GU愈合药物评估；溃疡愈合相关机制研究	通过乙酸灌胃模拟寒邪或热邪侵袭

方法 Methods	优点 Advantages	缺点 Disadvantages	适用范围 Range of application	病理 Pathology
幽门结扎法 Pyloric ligation method	GU重复性好，实验结果稳定；实验造成的GU部位明确，溃疡程度可控	人为结扎为非生理性GU；实验操作技术要求高	急性GU研究；用于抗GU药物评估；GU相关机制研究	通过胃酸堆积、压迫血管，模拟GU
水浸-束缚应激法 Water immersion-restraint stress method	GU复制率高，重复性好；实验操作简单；能较好模拟应激引发的GU	操作过程缺乏量化标准；可能引发其他生理变化；个体差异影响较大；仅适用于短期研究	应激性GU研究；用于抗应激性GU药物评估；应激反应机制研究	通过束缚、水浸，模拟情志失调模型
乙醇诱导法 Ethanol-induced method	操作方法简单，重复性好，成模效果好；能短时间诱导胃黏膜损伤；GU溃疡程度可控	直接损伤胃黏膜为非生理性溃疡；不适用于长期慢性GU研究；死亡率较高	急性GU研究；用于抗GU、胃黏膜保护药物评估；胃黏膜屏障功能机制研究	通过乙醇灌胃，模拟寒邪或热邪侵袭
乙酸诱导法 Acetic acid-induced method	GU形成后持续时间长，重复性好；造模方法简单；溃疡程度可控	直接损伤胃黏膜为非生理性溃疡；诱导GU局限于慢性GU	慢性GU研究；用于促GU愈合药物评估；溃疡愈合相关机制研究	通过乙酸灌胃模拟寒邪或热邪侵袭

方法 Methods	优点 Advantages	缺点 Disadvantages	适用范围 Range of application	病因病机 Pathogenesis
饮食失节法 Eating disorder method	符合中医病因病机理论；造模方法简单；实验结果稳定	建模周期较长；可能引发其他生理变化；个体差异影响较大	中医证候研究；用于中药疗效的研发与评估；脾胃消化相关机制研究	通过脾胃功能失调，消化系统紊乱，引发疾病
苦寒泻下法 Bitter-cold purging method	造模方法简单；建模周期较短；模型严重程度可控；标准化程度高；模型可通过药物反证验证	病理因素单一，难以模拟自然多因素病情；可能引起其他生理变化；个体差异影响较大；模型局限于短期研究	中医证候研究；用于中药疗效的研发与评估；脾胃消化相关机制研究	通过药物使脾胃阳气受损，引发脾胃衰虚，导致腹痛泻下
过度劳倦法 Excessive fatigue method	可控制劳动程度及劳动时长；可重复性强；病理相关指标关联性强	需精准控制运动强度和精神刺激；模型指标难以量化；可能引发全身性应激反应	中医证候研究；慢性疲劳综合研究；情志致病理论研究；脾胃消化、免疫相关机制研究	通过过度劳倦使气血耗伤，脏腑功能失调，引发脾胃虚寒
耗气破气法 Qi consumption and Qi impairment method	符合中医病因病机理论；实验条件简单，周期较短，易标准化；模型症状与临床症状吻合度高	造成脾胃虚寒程度较轻；可能引起其他生理变化	中医证候研究；用于中药疗效的研发与评估；脾胃消化相关机制研究	通过损耗机体正气，使气机失调，破气泄泻，引发脾胃虚寒
过食酸味法 Overeating sour-flavor method	符合中医病因病机理论；操作简单，成本较低；实验贴近真实病理过程，模型与临床症状吻合度高	模型稳定性差，模型指标难以量化；可能引起其他生理变化	中医证候研究；用于中药疗效的研发与评估；脾胃消化相关机制研究	通过过度食用酸味食物和药物，使脏腑功能失调，损伤脾胃，导致脾胃虚寒

方法 Methods	优点 Advantages	缺点 Disadvantages	适用范围 Range of application	病因病机 Pathogenesis
饮食失节法 Eating disorder method	符合中医病因病机理论；造模方法简单；实验结果稳定	建模周期较长；可能引发其他生理变化；个体差异影响较大	中医证候研究；用于中药疗效的研发与评估；脾胃消化相关机制研究	通过脾胃功能失调，消化系统紊乱，引发疾病
苦寒泻下法 Bitter-cold purging method	造模方法简单；建模周期较短；模型严重程度可控；标准化程度高；模型可通过药物反证验证	病理因素单一，难以模拟自然多因素病情；可能引起其他生理变化；个体差异影响较大；模型局限于短期研究	中医证候研究；用于中药疗效的研发与评估；脾胃消化相关机制研究	通过药物使脾胃阳气受损，引发脾胃衰虚，导致腹痛泻下
过度劳倦法 Excessive fatigue method	可控制劳动程度及劳动时长；可重复性强；病理相关指标关联性强	需精准控制运动强度和精神刺激；模型指标难以量化；可能引发全身性应激反应	中医证候研究；慢性疲劳综合研究；情志致病理论研究；脾胃消化、免疫相关机制研究	通过过度劳倦使气血耗伤，脏腑功能失调，引发脾胃虚寒
耗气破气法 Qi consumption and Qi impairment method	符合中医病因病机理论；实验条件简单，周期较短，易标准化；模型症状与临床症状吻合度高	造成脾胃虚寒程度较轻；可能引起其他生理变化	中医证候研究；用于中药疗效的研发与评估；脾胃消化相关机制研究	通过损耗机体正气，使气机失调，破气泄泻，引发脾胃虚寒
过食酸味法 Overeating sour-flavor method	符合中医病因病机理论；操作简单，成本较低；实验贴近真实病理过程，模型与临床症状吻合度高	模型稳定性差，模型指标难以量化；可能引起其他生理变化	中医证候研究；用于中药疗效的研发与评估；脾胃消化相关机制研究	通过过度食用酸味食物和药物，使脏腑功能失调，损伤脾胃，导致脾胃虚寒

造模方法 Modeling methods	具体方法 Experimental methods	动物 Animals	参考文献 References	优点 Advantages	缺点 Disadvantages
双因素造模 Two-factor modeling	过食酸味+乙醇	SD大鼠	[41]	操作简单；病理特征明显；成本较低	病理机制单一；稳定性较差；仅适用于初步研究
	苦寒泻下+冰醋酸	SD大鼠	[43]
	苦寒泻下+冰乙酸	SD大鼠	[44]
三因素造模 Three-factor modeling	苦寒泻下+劳倦过度+乙醇、阿司匹林	SD大鼠	[9]	病理机制全面；稳定性和可重复性高；更贴合实际临床；适用于深入研究	实验操作复杂，实验周期长；成本较高；多种因素叠加动物死亡率高
	饮食失节+苦寒泻下+冰乙酸	Wistar大鼠	[29]
	耗气破气+饮食失节+冰醋酸	成年大鼠	[36]
	饮食失节+过食酸味+醋酸涂抹	Wistar大鼠	[40]