 
  
			 
 
			 
 
			 
 
			 
 
			 
 
		实验动物与比较医学 ›› 2025, Vol. 45 ›› Issue (5): 596-610.DOI: 10.12300/j.issn.1674-5817.2025.038
        
               		王笑铭1, 孟晨晨1, 范鹿1, 李艳阳2, 张军平1, 吕仕超1( )(
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收稿日期:2025-03-13
									
				
											修回日期:2025-06-07
									
				
									
				
											出版日期:2025-10-25
									
				
											发布日期:2025-10-23
									
			通讯作者:
					作者简介:王笑铭(1998—),女,硕士研究生,研究方向:中医药防治心血管疾病。E-mail:13513912077@163.com
				
							基金资助:
        
               		WANG Xiaoming1, MENG Chenchen1, FAN Lu1, LI Yanyang2, ZHANG Junping1, LÜ Shichao1( )(
)( )
)
			  
			
			
			
                
        
    
Received:2025-03-13
									
				
											Revised:2025-06-07
									
				
									
				
											Published:2025-10-25
									
				
											Online:2025-10-23
									
			Contact:
					LÜ Shichao (ORCID: 0000-0002-4073-9083), E-mail: 372272027@qq.com摘要:
探讨中医证候动物模型不同的构建方法及其优劣势,并针对现有构建方法存在的问题提出优化策略,以期为构建既保有中医证候本质又符合现代科研规范的中医证候动物模型提供参考。本文以“中医”“证候”“动物模型”为关键词检索并阅览知网、万方以及维普数据库中有关中医证候动物模型的文章,继而系统梳理了当前中医证候动物模型主要构建方法的理论依据、技术特点及存在问题,并针对存在的问题提出相应的优化措施。中医证候动物模型的构建方法包括中医病因病机构建法、现代医学病因病理构建法以及中西医病证结合构建法。中医病因病机构建法以整体观为指导,通过模拟六淫致病、情志失调等外因来构建证候模型;该方法虽契合中医理论内涵、操作简便且可控性强,但存在造模成功率低、病因-证候拟合度不足等问题。现代医学病因病理构建法基于微观病理机制,采用药物干预、手术建模等可控性强的技术手段;该方法虽具有客观指标明确、可重复性优的特点,但存在偏离中医“证”的本质、安全性不足等缺陷。中西医病证结合法在证候本质还原度与技术可行性上呈显著互补性,在方法论上实现了中医基础理论与临床辨证思维的系统融合,并整合现代医学的客观评价体系,提升了西医病理机制与中医证候演变规律的临床吻合度;然而,该方法仍面临证候辨识标准模糊、疾病进展模拟失真等共性挑战。中医证候动物模型的构建虽面临理论适配性差、技术标准化欠佳等问题,但在验证方药疗效和推动中医药国际化方面仍具有不可替代的价值。未来应通过优化动物选择、完善制备方法理论依据、规范造模因素设置、明确造模成功标准等措施优化中医证候动物模型的构建。
中图分类号:
王笑铭,孟晨晨,范鹿,等. 中医证候类动物模型构建方法概述[J]. 实验动物与比较医学, 2025, 45(5): 596-610. DOI: 10.12300/j.issn.1674-5817.2025.038.
WANG Xiaoming,MENG Chenchen,FAN Lu,et al. An Overview of Strategies for Constructing Animal Models of Traditional Chinese Medicine Syndromes[J]. Laboratory Animal and Comparative Medicine, 2025, 45(5): 596-610. DOI: 10.12300/j.issn.1674-5817.2025.038.
| 造模方法 Construction methods | 实验动物选择 Laboratory animal selections | 作用机制 Mechanisms | 中医证型 Traditional Chinese medicine syndromes | 
|---|---|---|---|
| 寒冷刺激加风扇吹风法[ Cold stimulation plus fan blowing[ | 雄性SD大鼠 | 外感风寒,阻滞卫阳 | 风寒表证 | 
| 寒冷刺激加潮湿环境法[ Cold stimulation plus humid environment[ | 雄性KM小鼠 | 外感风寒湿,郁遏肌肤 | 风寒湿证 | 
| 冰水浴法[ Ice-water bath[ | 雌性SD大鼠 | 寒邪侵袭,寒性凝滞,血为寒凝 | 寒凝血瘀证 | 
| 湿热环境刺激法[ Humid and hot environment stimulation[ | 雄性SD大鼠 | 外感湿热,阻滞皮肤,发为湿热 | 湿热证 | 
| 热应激法[ Heat stress[ | 雄性SD大鼠 | 热盛伤阴,发为阴虚 | 阴虚证 | 
| 慢性不可预知温和应激法[ Chronic unpredictable mild stress[ | 雄性SD大鼠 | 肝气郁结,横乘脾土 | 肝郁脾虚证 | 
| 慢性束缚性应激法[ Chronic restraint stress[ | 雄性SD大鼠 | 肝失疏泄,阻滞气机 | 肝郁气滞证 | 
| 猫吓鼠[ "Cat scared rat"[ | SD仔鼠,雌雄各半 | 恐为肾志,恐则气下,过度惊恐导致肾虚 | 肾虚证 | 
| 负重力竭游泳法[ Forced swimming[ | 雄性SD大鼠 | 劳则气耗,发为气虚 | 气虚证 | 
| 水环境小平台睡眠剥夺法[ Platform and sleep deprivation[ | 雄性SD大鼠 | 寐不得安,劳耗心神,心主神明,损及心气 | 心气虚证 | 
| 房事不节法[ Sexual overstrain[ | 雄性KM小鼠 | 房事不节,耗竭肾精,精不化阳,肾阳亏虚 | 肾阳虚证 | 
| 长期力竭游泳法[ Long-term forced swimming[ | 雄性SD大鼠 | 过劳伤阴,阴不制阳,发为内热 | 阴虚内热证 | 
| 饮食失节法[ Diet disorder[ | 雄性C57小鼠 | 饮食失节,损伤脾胃,气不化生,发为脾虚 | 脾虚型 | 
| 高脂饮食法[ High-fat feeding[ | 雌性BALB/c小鼠 | 嗜食肥甘厚腻,壅滞脾胃,运化失职,痰浊凝聚 | 痰证 | 
| 偏食法[ Partial feeding[ | 雄性Wistar大鼠 | 味过于酸,肝气以津,脾气乃绝 | 脾气虚证 | 
| 自然衰老法[ Natural aging[ | 雄性SD大鼠 | 八八,天癸竭,精少,肾藏精,精化气,肾精亏虚 | 肾虚证 | 
| 恐惧情志失调法联合低温环境致病法[ Fear-mongering method combined with cryogenic environment[ | 雄性SD大鼠 | 恐伤肾,寒伤阳 | 肾阳虚证 | 
| 饮食失节联合劳倦过度法[ Irregular diet and overwork[ | SD仔鼠,雌雄各半 | 饮食失节伤脾,劳则耗气,二者结合,发为脾气虚证 | 脾气虚证 | 
| 慢性束缚性应激联合过度疲劳、饮食失节法[ Chronic restraint stress, excessive fatigue and diet failure[ | SD大鼠,雌雄各半 | 肝失疏泄,气机郁滞,发为肝郁;劳则耗气,饮食失节伤脾,导致脾气虚弱。二者相合,则为肝郁脾虚 | 肝郁脾虚证 | 
表1 常见的中医病因病机构建方法、实验动物选择、作用机制以及中医证型
Table 1 Common construction methods, laboratory animal selections, mechanisms, and traditional Chinese medicine syndromes of etiology and pathogenesis of traditional Chinese medicine
| 造模方法 Construction methods | 实验动物选择 Laboratory animal selections | 作用机制 Mechanisms | 中医证型 Traditional Chinese medicine syndromes | 
|---|---|---|---|
| 寒冷刺激加风扇吹风法[ Cold stimulation plus fan blowing[ | 雄性SD大鼠 | 外感风寒,阻滞卫阳 | 风寒表证 | 
| 寒冷刺激加潮湿环境法[ Cold stimulation plus humid environment[ | 雄性KM小鼠 | 外感风寒湿,郁遏肌肤 | 风寒湿证 | 
| 冰水浴法[ Ice-water bath[ | 雌性SD大鼠 | 寒邪侵袭,寒性凝滞,血为寒凝 | 寒凝血瘀证 | 
| 湿热环境刺激法[ Humid and hot environment stimulation[ | 雄性SD大鼠 | 外感湿热,阻滞皮肤,发为湿热 | 湿热证 | 
| 热应激法[ Heat stress[ | 雄性SD大鼠 | 热盛伤阴,发为阴虚 | 阴虚证 | 
| 慢性不可预知温和应激法[ Chronic unpredictable mild stress[ | 雄性SD大鼠 | 肝气郁结,横乘脾土 | 肝郁脾虚证 | 
| 慢性束缚性应激法[ Chronic restraint stress[ | 雄性SD大鼠 | 肝失疏泄,阻滞气机 | 肝郁气滞证 | 
| 猫吓鼠[ "Cat scared rat"[ | SD仔鼠,雌雄各半 | 恐为肾志,恐则气下,过度惊恐导致肾虚 | 肾虚证 | 
| 负重力竭游泳法[ Forced swimming[ | 雄性SD大鼠 | 劳则气耗,发为气虚 | 气虚证 | 
| 水环境小平台睡眠剥夺法[ Platform and sleep deprivation[ | 雄性SD大鼠 | 寐不得安,劳耗心神,心主神明,损及心气 | 心气虚证 | 
| 房事不节法[ Sexual overstrain[ | 雄性KM小鼠 | 房事不节,耗竭肾精,精不化阳,肾阳亏虚 | 肾阳虚证 | 
| 长期力竭游泳法[ Long-term forced swimming[ | 雄性SD大鼠 | 过劳伤阴,阴不制阳,发为内热 | 阴虚内热证 | 
| 饮食失节法[ Diet disorder[ | 雄性C57小鼠 | 饮食失节,损伤脾胃,气不化生,发为脾虚 | 脾虚型 | 
| 高脂饮食法[ High-fat feeding[ | 雌性BALB/c小鼠 | 嗜食肥甘厚腻,壅滞脾胃,运化失职,痰浊凝聚 | 痰证 | 
| 偏食法[ Partial feeding[ | 雄性Wistar大鼠 | 味过于酸,肝气以津,脾气乃绝 | 脾气虚证 | 
| 自然衰老法[ Natural aging[ | 雄性SD大鼠 | 八八,天癸竭,精少,肾藏精,精化气,肾精亏虚 | 肾虚证 | 
| 恐惧情志失调法联合低温环境致病法[ Fear-mongering method combined with cryogenic environment[ | 雄性SD大鼠 | 恐伤肾,寒伤阳 | 肾阳虚证 | 
| 饮食失节联合劳倦过度法[ Irregular diet and overwork[ | SD仔鼠,雌雄各半 | 饮食失节伤脾,劳则耗气,二者结合,发为脾气虚证 | 脾气虚证 | 
| 慢性束缚性应激联合过度疲劳、饮食失节法[ Chronic restraint stress, excessive fatigue and diet failure[ | SD大鼠,雌雄各半 | 肝失疏泄,气机郁滞,发为肝郁;劳则耗气,饮食失节伤脾,导致脾气虚弱。二者相合,则为肝郁脾虚 | 肝郁脾虚证 | 
| 造模方法 Construction methods | 实验动物选择 Laboratory animal selections | 作用机制 Mechanisms | 中医证型 Traditional Chinese medicine syndromes | 
|---|---|---|---|
| 肌内注射氢化可的松法[ Intramuscular hydrocortisone injection[ | 雄性SD大鼠 | 抑制促肾上腺激素及肾上腺素的分泌,导致机体出现体重下降、萎靡、耐寒力低等肾阳虚证的症候群 | 肾阳虚证 | 
| 灌胃甲状腺片法[ Gavage thyroid tablet[ | 雄性KM小鼠 | 甲状腺素含量升高,促进机体分解蛋白质、糖原和脂肪,导致机体基础代谢率升高,产热量增加,体温升高,体重下降 | 阴虚证、 虚热证 | 
| 腹腔注射环磷酰胺法[ Intraperitoneal cyclophosphamide injection[ | KM小鼠,雌雄各半 | 抑制骨髓造血功能 | 血虚证 | 
| 皮下注射乙酰苯肼法[ Subcutaneous injection of acetylphenylhydrazine[ | 雄性Wistar大鼠 | 干扰葡萄糖-6-磷酸脱氢酶对红细胞膜造成氧化损伤,造成溶血性贫血 | 血虚证 | 
| 皮下注射肾上腺素法[ Subcutaneous injection of epinephrine[ | 雄性SD大鼠 | 机体儿茶酚胺含量变化引发焦虑,肝气郁结,肝失疏泄,血液运行不畅 | 气滞血瘀证 | 
| 冠状动脉结扎法[ Coronary ligation[ | 雄性SD大鼠 | 血运失畅,心脉瘀阻 | 血瘀证 | 
| Ameroid缩窄环压迫冠状动脉法[ Ameroid stenotic ring compression of coronary artery [ | 中华小型猪 | 缩窄环缓慢膨胀,压迫冠状动脉,阻碍血行 | 血瘀证 | 
| 去势法——切除性腺法[ Castration-removal of the gonad[ | 雌性SD大鼠 | 下丘脑-垂体-性腺轴功能紊乱,性激素分泌失调,基础代谢及体温调节能力下降,出现畏寒肢冷等肾阳虚证的症候群 | 肾阳虚证 | 
| 烟叶加刨花烟熏刺激法[ Smoke-stimulated method of tobacco leaf and wood shavings[ | SD大鼠,雌雄各半 | 模仿空气污染,诱导肺、气管及支气管发生氧化应激和炎症反应,耗伤肺气 | 肺气虚证 | 
| 60Coγ射线全身照射法[ Whole body irradiation of 60Coγ[ | 雌性C57BL/6J 小鼠[ | 电离辐射诱导骨髓造血功能障碍,血液生成乏源 | 血虚证 | 
| 雌性SD大鼠[ | 电离辐射损伤骨髓,继而精不化血、髓海空虚,而肾主骨生髓,导致肾精不充 | 肾精亏虚证 | |
| 腹腔注射脂多糖法[ Intraperitoneal injection of lipopolysaccharides[ | 雄性SD大鼠 | 外邪入侵、热盛为毒,热毒炽盛、炼血成瘀 | 热毒血瘀证 | 
| 高脂高糖饮食、湿热环境联合感染登革病毒法[ High-fat and high-sugar diet, damp and hot environment combined infection dengue virus[ | BALB/c和C57BL/6 小鼠,雌雄各半 | 外感湿热,外湿引动内湿,加之病毒在机体内刺激炎症发生,促进形成湿热证 | 湿热证 | 
表2 常见的现代医学病因病理构建方法、实验动物选择、作用机制以及中医证型
Table 2 Common construction methods, laboratory animal selections, mechanisms, and traditional Chinese medicine syndromes of etiology and pathology of modern medicine
| 造模方法 Construction methods | 实验动物选择 Laboratory animal selections | 作用机制 Mechanisms | 中医证型 Traditional Chinese medicine syndromes | 
|---|---|---|---|
| 肌内注射氢化可的松法[ Intramuscular hydrocortisone injection[ | 雄性SD大鼠 | 抑制促肾上腺激素及肾上腺素的分泌,导致机体出现体重下降、萎靡、耐寒力低等肾阳虚证的症候群 | 肾阳虚证 | 
| 灌胃甲状腺片法[ Gavage thyroid tablet[ | 雄性KM小鼠 | 甲状腺素含量升高,促进机体分解蛋白质、糖原和脂肪,导致机体基础代谢率升高,产热量增加,体温升高,体重下降 | 阴虚证、 虚热证 | 
| 腹腔注射环磷酰胺法[ Intraperitoneal cyclophosphamide injection[ | KM小鼠,雌雄各半 | 抑制骨髓造血功能 | 血虚证 | 
| 皮下注射乙酰苯肼法[ Subcutaneous injection of acetylphenylhydrazine[ | 雄性Wistar大鼠 | 干扰葡萄糖-6-磷酸脱氢酶对红细胞膜造成氧化损伤,造成溶血性贫血 | 血虚证 | 
| 皮下注射肾上腺素法[ Subcutaneous injection of epinephrine[ | 雄性SD大鼠 | 机体儿茶酚胺含量变化引发焦虑,肝气郁结,肝失疏泄,血液运行不畅 | 气滞血瘀证 | 
| 冠状动脉结扎法[ Coronary ligation[ | 雄性SD大鼠 | 血运失畅,心脉瘀阻 | 血瘀证 | 
| Ameroid缩窄环压迫冠状动脉法[ Ameroid stenotic ring compression of coronary artery [ | 中华小型猪 | 缩窄环缓慢膨胀,压迫冠状动脉,阻碍血行 | 血瘀证 | 
| 去势法——切除性腺法[ Castration-removal of the gonad[ | 雌性SD大鼠 | 下丘脑-垂体-性腺轴功能紊乱,性激素分泌失调,基础代谢及体温调节能力下降,出现畏寒肢冷等肾阳虚证的症候群 | 肾阳虚证 | 
| 烟叶加刨花烟熏刺激法[ Smoke-stimulated method of tobacco leaf and wood shavings[ | SD大鼠,雌雄各半 | 模仿空气污染,诱导肺、气管及支气管发生氧化应激和炎症反应,耗伤肺气 | 肺气虚证 | 
| 60Coγ射线全身照射法[ Whole body irradiation of 60Coγ[ | 雌性C57BL/6J 小鼠[ | 电离辐射诱导骨髓造血功能障碍,血液生成乏源 | 血虚证 | 
| 雌性SD大鼠[ | 电离辐射损伤骨髓,继而精不化血、髓海空虚,而肾主骨生髓,导致肾精不充 | 肾精亏虚证 | |
| 腹腔注射脂多糖法[ Intraperitoneal injection of lipopolysaccharides[ | 雄性SD大鼠 | 外邪入侵、热盛为毒,热毒炽盛、炼血成瘀 | 热毒血瘀证 | 
| 高脂高糖饮食、湿热环境联合感染登革病毒法[ High-fat and high-sugar diet, damp and hot environment combined infection dengue virus[ | BALB/c和C57BL/6 小鼠,雌雄各半 | 外感湿热,外湿引动内湿,加之病毒在机体内刺激炎症发生,促进形成湿热证 | 湿热证 | 
| 造模方法 Construction methods | 实验动物选择 Laboratory animal selections | 作用机制 Mechanisms | 中医证型 Traditional Chinese medicine syndromes | 
|---|---|---|---|
| 异硫氰酸萘酯灌胃法结合湿热环境法、高糖高脂饮食法[ Oral administration of α-naphthyl isothiocyanate along with the hot and humid environment and high-fat and high-carbohydrate diet[ | 雄性SD大鼠 | 异硫氰酸萘酯灌胃强化肝损伤,胆红素代谢障碍,导致黄疸;外感湿热之邪、高糖高脂的饮食因素诱发脾胃气机失调、湿热内蕴,引起阳黄证 | 黄疸阳黄证 | 
| 冠状动脉结扎法联合高脂饮食法[ Coronary artery ligation combined with a high-fat feeding diet[ | 雄性Wistar大鼠 | 冠状动脉结扎直接阻断血流,血行不畅,瘀阻脉络,符合“瘀证”;高脂饮食导致痰浊内生,壅塞脉道,阻滞气机,形成“痰证”;二者结合,形成痰瘀互结证 | 冠心病痰瘀互结证 | 
| 灌服盐酸普萘洛尔法联合负重力竭游泳运动法[ Oral administration of propranolol hydrochloride solution and weight-loaded exhaustive swimming[ | 雄性KM小鼠 | 盐酸普萘洛尔减慢心率、抑制心脏收缩力;过劳伤脾,脾胃虚弱,气血生化无源;二者结合,导致心神失养,发为心脾两虚证失眠 | 失眠心脾两虚证 | 
| 病毒滴鼻感染法联合湿热环境法[ External damp-heat stimulation and viral intranasal infection[ | BALB/c小鼠,雌雄各半 | 滴鼻感染直接侵袭呼吸道黏膜上皮细胞;疫毒外侵,正气亏虚,肺脏受邪;湿性黏滞、热性炎上,湿热环境导致气机壅滞,津液输布失常,湿热内蕴,熏蒸肺卫,发为湿热疫 | 人冠状病毒肺炎湿热疫毒袭肺证 | 
| 皮内注射Ⅱ型胶原法结合寒湿环境法(或湿热环境法)[ Intradermal injection of type Ⅱ collagen combined with the cold and damp environment (or hot and humid environment)[ | Wistar大鼠 | Ⅱ型胶血管翳形成及软骨破坏,寒湿侵袭关节,寒性收引、湿性黏滞,导致经络闭阻、气血运行不畅,形成寒湿痹证 | 类风湿关节炎寒湿证 | 
| Ⅱ型胶血管翳形成及软骨破坏,湿热内蕴,熏蒸关节,炼液成痰、灼血成瘀,瘀则不通,不通则痛,发为湿热痹证 | 类风湿关节炎湿热证 | 
表3 常见的中西医病证结合构建方法、实验动物选择、作用机制以及中医证型
Table 3 Common construction methods, laboratory animal selections, mechanisms, and traditional Chinese medicine syndromes of integration of traditional Chinese medicine and Western medicine for diseases and syndromes
| 造模方法 Construction methods | 实验动物选择 Laboratory animal selections | 作用机制 Mechanisms | 中医证型 Traditional Chinese medicine syndromes | 
|---|---|---|---|
| 异硫氰酸萘酯灌胃法结合湿热环境法、高糖高脂饮食法[ Oral administration of α-naphthyl isothiocyanate along with the hot and humid environment and high-fat and high-carbohydrate diet[ | 雄性SD大鼠 | 异硫氰酸萘酯灌胃强化肝损伤,胆红素代谢障碍,导致黄疸;外感湿热之邪、高糖高脂的饮食因素诱发脾胃气机失调、湿热内蕴,引起阳黄证 | 黄疸阳黄证 | 
| 冠状动脉结扎法联合高脂饮食法[ Coronary artery ligation combined with a high-fat feeding diet[ | 雄性Wistar大鼠 | 冠状动脉结扎直接阻断血流,血行不畅,瘀阻脉络,符合“瘀证”;高脂饮食导致痰浊内生,壅塞脉道,阻滞气机,形成“痰证”;二者结合,形成痰瘀互结证 | 冠心病痰瘀互结证 | 
| 灌服盐酸普萘洛尔法联合负重力竭游泳运动法[ Oral administration of propranolol hydrochloride solution and weight-loaded exhaustive swimming[ | 雄性KM小鼠 | 盐酸普萘洛尔减慢心率、抑制心脏收缩力;过劳伤脾,脾胃虚弱,气血生化无源;二者结合,导致心神失养,发为心脾两虚证失眠 | 失眠心脾两虚证 | 
| 病毒滴鼻感染法联合湿热环境法[ External damp-heat stimulation and viral intranasal infection[ | BALB/c小鼠,雌雄各半 | 滴鼻感染直接侵袭呼吸道黏膜上皮细胞;疫毒外侵,正气亏虚,肺脏受邪;湿性黏滞、热性炎上,湿热环境导致气机壅滞,津液输布失常,湿热内蕴,熏蒸肺卫,发为湿热疫 | 人冠状病毒肺炎湿热疫毒袭肺证 | 
| 皮内注射Ⅱ型胶原法结合寒湿环境法(或湿热环境法)[ Intradermal injection of type Ⅱ collagen combined with the cold and damp environment (or hot and humid environment)[ | Wistar大鼠 | Ⅱ型胶血管翳形成及软骨破坏,寒湿侵袭关节,寒性收引、湿性黏滞,导致经络闭阻、气血运行不畅,形成寒湿痹证 | 类风湿关节炎寒湿证 | 
| Ⅱ型胶血管翳形成及软骨破坏,湿热内蕴,熏蒸关节,炼液成痰、灼血成瘀,瘀则不通,不通则痛,发为湿热痹证 | 类风湿关节炎湿热证 | 
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