实验动物与比较医学 ›› 2026, Vol. 46 ›› Issue (4): 531-540.DOI: 10.12300/j.issn.1674-5817.2025.172
赵玉磊1(
), 韩冰冰1, 王兴鑫2, 杨广建3, 王雅杰3, 唐晓勇3(
)
收稿日期:2025-10-13
修回日期:2026-02-05
出版日期:2026-08-25
发布日期:2026-08-22
通讯作者:
唐晓勇(1977—),男,博士,主任医师,研究方向:肺癌的内科综合治疗和内科简易胸腔镜的诊断。E-mail:sdtangxiaoyong2025@163.com。ORCID:0009-0001-6580-3096
作者简介:赵玉磊(1996—),女,硕士,研究方向:中西医结合防治肿瘤基础研究。E-mail:2023110073@sdutcm.edu.cn。ORCID:0009-0006-5825-5382基金资助:
ZHAO Yulei1(
), HAN Bingbing1, WANG Xingxin2, YANG Guangjian3, WANG Yajie3, TANG Xiaoyong3(
)
Received:2025-10-13
Revised:2026-02-05
Published:2026-08-25
Online:2026-08-22
Correspondence to:
TANG Xiaoyong (ORCID: 0009-0001-6580-3096), E-mail: sdtangxiaoyong2025@163.com摘要:
肺癌是全球范围内病死率最高的恶性肿瘤,严重威胁人类健康。中医治疗肺癌具有独特优势,而病证结合动物模型是中医肺癌研究的关键环节。根据中医病因病机,肺癌属本虚标实之证,临床常分为气阴两虚证、肺脾气虚证、肺阴虚证、气滞血瘀证、痰热阻肺证等证型,治疗应以“扶正祛邪”为根本法则。本文系统检索了2005—2025年病证结合肺癌动物模型相关文献,总结了气阴两虚型、脾气虚型、气滞血瘀型、肾虚型4类核心病证结合模型的构建理论依据与制备方法,并进一步讨论了各自的评价体系及局限性。此外,本文还总结了阳虚型、脾虚型、气虚血瘀型等其他病证结合模型的造模方式,从行为学特征和生化指标归纳了模型评价方法。分析结果表明,当前模型多以C57BL/6小鼠为造模对象,存在临床吻合度不足、造模方法复杂、干扰因素多、标准化程度低等问题,提出了未来病证结合肺癌动物模型的改进方向:可利用成簇规律间隔短回文重复序列技术(clustered regularly interspaced short palindromic repeats,CRISPR)建立类器官-患者来源的异种移植物模型;构建可控性复合应激体系,开发如梯度温控寒热交替箱、程序化饮食调控系统等标准化刺激模块,减少非特异性干扰;在发展多维度动态造模技术方面,整合代谢组学、影像特征等临床大数据设计动态干预方案,为阐释中医防治肺癌作用机制提供更精准、更可靠的实验工具。
中图分类号:
赵玉磊,韩冰冰,王兴鑫,等. 病证结合肺癌小鼠模型研究进展[J]. 实验动物与比较医学, 2026, 46(4): 531-540. DOI: 10.12300/j.issn.1674-5817.2025.172.
ZHAO Yulei,HAN Bingbing,WANG Xingxin,et al. Progress in Disease-Syndrome-Integrated Mouse Models of Lung Cancer[J]. Laboratory Animal and Comparative Medicine, 2026, 46(4): 531-540. DOI: 10.12300/j.issn.1674-5817.2025.172.
证型 Syndrome pattern | 症状 Symptoms | 舌脉 Tongue and pulse | 治则 Treatment principles |
|---|---|---|---|
气阴两虚证 Qi and yin deficiency syndrome | ①咳嗽有痰或无痰;②神疲乏力;③汗出气短;④口干发热;⑤午后潮热;⑥手足心热;⑦有时心悸 | 舌质红苔薄或舌质胖大有齿痕,脉细 | 益气养阴 |
肺脾气虚证 Lung-spleen qi deficiency syndrome | ①久咳痰稀;②胸闷;③气短;④神疲乏力;⑤腹胀纳呆;⑥浮肿便溏 | 舌质淡、苔薄、边有齿痕,脉沉细 | 补肺健脾,益气 |
肺阴虚证 Lung yin deficiency syndrome | ①咳嗽气短;②干咳;③少痰;④潮热盗汗;⑤五心烦热;⑥口干口渴;⑦声音嘶哑 | 舌赤少苔或舌体瘦小、苔薄,脉细数 | 养阴润肺 |
气滞血瘀证 Qi stagnation and blood stasis syndrome | ①咳嗽气短而不爽;②气促胸闷;③心胸刺痛或胀痛;④痞块疼痛拒按;⑤唇暗 | 舌紫暗或有瘀血斑、苔薄,脉弦或涩 | 活血化瘀,行气止痛 |
痰热阻肺证 Phlegm-heat obstructing the lungs syndrome | ①痰多咳重;②痰黄黏稠;③气憋胸闷;④发热;⑤纳呆 | 舌质红、苔厚或黄,脉弦滑或兼数 | 清热化痰,降气止咳 |
表1 肺癌中医辨证分型
Table 1 Traditional Chinese medicine pattern differentiation of lung cancer
证型 Syndrome pattern | 症状 Symptoms | 舌脉 Tongue and pulse | 治则 Treatment principles |
|---|---|---|---|
气阴两虚证 Qi and yin deficiency syndrome | ①咳嗽有痰或无痰;②神疲乏力;③汗出气短;④口干发热;⑤午后潮热;⑥手足心热;⑦有时心悸 | 舌质红苔薄或舌质胖大有齿痕,脉细 | 益气养阴 |
肺脾气虚证 Lung-spleen qi deficiency syndrome | ①久咳痰稀;②胸闷;③气短;④神疲乏力;⑤腹胀纳呆;⑥浮肿便溏 | 舌质淡、苔薄、边有齿痕,脉沉细 | 补肺健脾,益气 |
肺阴虚证 Lung yin deficiency syndrome | ①咳嗽气短;②干咳;③少痰;④潮热盗汗;⑤五心烦热;⑥口干口渴;⑦声音嘶哑 | 舌赤少苔或舌体瘦小、苔薄,脉细数 | 养阴润肺 |
气滞血瘀证 Qi stagnation and blood stasis syndrome | ①咳嗽气短而不爽;②气促胸闷;③心胸刺痛或胀痛;④痞块疼痛拒按;⑤唇暗 | 舌紫暗或有瘀血斑、苔薄,脉弦或涩 | 活血化瘀,行气止痛 |
痰热阻肺证 Phlegm-heat obstructing the lungs syndrome | ①痰多咳重;②痰黄黏稠;③气憋胸闷;④发热;⑤纳呆 | 舌质红、苔厚或黄,脉弦滑或兼数 | 清热化痰,降气止咳 |
证型 Syndrome type | 动物品系 Animal strain | 造模方式 Modeling method | 造模时间 Modeling duration | 模型评价 Model evaluation |
|---|---|---|---|---|
阳虚型[ Yang deficiency pattern[ | C57BL/6小鼠(雄性) | 肌肉注射氢化可的松+腋下皮下接种Lewis细胞悬液 | 21 d | 小鼠畏寒肢冷、活动减少、精神萎靡、食欲下降、皮毛暗淡、大便溏稀,症状评分显著升高。环磷酸腺苷水平下降、环磷酸鸟苷水平升高、环磷酸腺苷/环磷酸鸟苷比值降低,血清三碘甲状腺原氨酸含量下降。肿瘤组织生长迅速,可扪及肿块 |
脾虚型[ Spleen deficiency pattern[ | C57BL/6J小鼠(雌雄各半/雄性) | 小承气汤+隔日禁食+高脂饮食+过度疲劳+腋下皮下接种Lewis细胞悬液 | 21 d | 小鼠体重减轻、食量减少、便溏、运动耐力下降、活动减少、肌力减弱、毛发粗糙、畏寒。血清D-木糖吸收率<10%,胃泌素含量<50 pg/mL,白细胞介素-2水平显著降低,可扪及肿块 |
气虚血瘀型[ Qi deficiency and blood stasis pattern[ | C57BL/6小鼠(雄性) | 疲劳+惊恐+高脂饮食+腋下皮下接种Lewis细胞悬液 | 15 d | 小鼠倦怠、活动减少、体重下降、气短、毛发稀疏、舌暗、尾瘀斑。血浆黏度显著升高,血浆凝血酶原时间、活化部分凝血活酶时间及血浆纤维蛋白原水平均显著降低,可扪及肿块 |
肺肾两虚型[ Lung-kidney deficiency pattern[ | C57BL/6小鼠(雄性) | 烟熏+腹腔注射氢化可的松+腋下皮下接种Lewis细胞悬液 | 14 d | 小鼠毛发暗淡、眼睑下垂、缩肩拱背、自主活动减少、肌力减退、尿量增多、垂尾。血清中的白细胞介素-1、丙二醛含量升高,环磷酸腺苷水平下降、环磷酸鸟苷水平升高、环磷酸腺苷/环磷酸鸟苷比值降低,血清三碘甲状腺原氨酸含量下降,可扪及肿块 |
寒热错杂型[ Mixed cold-heat pattern[ | C57BL/6小鼠(雄性) | 丙硫氧嘧啶+知母石膏水煎液+番泻叶灌胃+冰水游泳+皮下注射干酵母混悬液+腋下皮下接种Lewis细胞悬液 | 35 d | 小鼠体温下降、粪便含水量升高、蜷缩扎堆、少动嗜卧、毛发枯槁、形体消瘦。血清三碘甲状腺原氨酸与四碘甲状腺原氨酸水平降低,超氧化物歧化酶与丙二醛含量均降低,可扪及肿块 |
表2 常见病证结合动物模型总结
Table 2 Summary of common disease-syndrome-integrated animal models
证型 Syndrome type | 动物品系 Animal strain | 造模方式 Modeling method | 造模时间 Modeling duration | 模型评价 Model evaluation |
|---|---|---|---|---|
阳虚型[ Yang deficiency pattern[ | C57BL/6小鼠(雄性) | 肌肉注射氢化可的松+腋下皮下接种Lewis细胞悬液 | 21 d | 小鼠畏寒肢冷、活动减少、精神萎靡、食欲下降、皮毛暗淡、大便溏稀,症状评分显著升高。环磷酸腺苷水平下降、环磷酸鸟苷水平升高、环磷酸腺苷/环磷酸鸟苷比值降低,血清三碘甲状腺原氨酸含量下降。肿瘤组织生长迅速,可扪及肿块 |
脾虚型[ Spleen deficiency pattern[ | C57BL/6J小鼠(雌雄各半/雄性) | 小承气汤+隔日禁食+高脂饮食+过度疲劳+腋下皮下接种Lewis细胞悬液 | 21 d | 小鼠体重减轻、食量减少、便溏、运动耐力下降、活动减少、肌力减弱、毛发粗糙、畏寒。血清D-木糖吸收率<10%,胃泌素含量<50 pg/mL,白细胞介素-2水平显著降低,可扪及肿块 |
气虚血瘀型[ Qi deficiency and blood stasis pattern[ | C57BL/6小鼠(雄性) | 疲劳+惊恐+高脂饮食+腋下皮下接种Lewis细胞悬液 | 15 d | 小鼠倦怠、活动减少、体重下降、气短、毛发稀疏、舌暗、尾瘀斑。血浆黏度显著升高,血浆凝血酶原时间、活化部分凝血活酶时间及血浆纤维蛋白原水平均显著降低,可扪及肿块 |
肺肾两虚型[ Lung-kidney deficiency pattern[ | C57BL/6小鼠(雄性) | 烟熏+腹腔注射氢化可的松+腋下皮下接种Lewis细胞悬液 | 14 d | 小鼠毛发暗淡、眼睑下垂、缩肩拱背、自主活动减少、肌力减退、尿量增多、垂尾。血清中的白细胞介素-1、丙二醛含量升高,环磷酸腺苷水平下降、环磷酸鸟苷水平升高、环磷酸腺苷/环磷酸鸟苷比值降低,血清三碘甲状腺原氨酸含量下降,可扪及肿块 |
寒热错杂型[ Mixed cold-heat pattern[ | C57BL/6小鼠(雄性) | 丙硫氧嘧啶+知母石膏水煎液+番泻叶灌胃+冰水游泳+皮下注射干酵母混悬液+腋下皮下接种Lewis细胞悬液 | 35 d | 小鼠体温下降、粪便含水量升高、蜷缩扎堆、少动嗜卧、毛发枯槁、形体消瘦。血清三碘甲状腺原氨酸与四碘甲状腺原氨酸水平降低,超氧化物歧化酶与丙二醛含量均降低,可扪及肿块 |
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