中国实验动物学报

不同剂量多柔比星诱导衰老小鼠模型的构建

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颜宏 ¹^,²^,³ , 龚吕东 ¹^,²^,³ , 钟承志 ¹^,²^,³ , 资志达 ¹^,²^,³ , 李婷 ¹^,²^,³ , 吴德松 ¹^,²^,³ , 郭琰 ¹^,²^,³^,^*

中国实验动物学报 | 研究报告 2026,34(3): 371-381

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中国实验动物学报 |研究报告 2026 , 34 (3) : 371 -381

不同剂量多柔比星诱导衰老小鼠模型的构建

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颜宏¹^,²^,³, 龚吕东¹^,²^,³, 钟承志¹^,²^,³, 资志达¹^,²^,³, 李婷¹^,²^,³, 吴德松¹^,²^,³, 郭琰¹^,²^,³^,^*

作者信息

^1．云南白药集团股份有限公司，昆明　650500

^2．云南省药物研究所，昆明　650111

^3．云南省中药和民族药新药创制企业重点实验室，昆明　650111

通讯作者:

郭琰，男，博士，正高级工程师，研究方向：中药、民族药药效活性研究和新药研发。Email：yaoxueguoyan@126.com

作者简介:

颜宏，男，学士，工程师，研究方向：中药药理与药效机制。Email：yanhong@ynby.cn

Construction of an aging mouse model induced by different doses of doxorubicin

Hong YAN¹^,²^,³, Lyudong GONG¹^,²^,³, Chengzhi ZHONG¹^,²^,³, Zhida ZI¹^,²^,³, Ting LI¹^,²^,³, Desong WU¹^,²^,³, Yan GUO¹^,²^,³^,^*

Affiliations

^1.Yunnan Baiyao Group Co., Ltd., Kunming 650500, China

^2.Yunnan Institute of Materia Medica, Kunming 650111, China

^3.Yunnan Province Company Key Laboratory for TCM and Ethnic Drug of New Drug Creation, Kunming 650111, China

Corresponding Author:

GUO Yan. E-mail: yaoxueguoyan@126.com

出版时间: 2026-03-30 doi: 10.3969/j.issn.1005-4847.2026.03.006

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摘要

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目的

通过不同剂量不同频次腹腔注射多柔比星（DOX）建立快速衰老小鼠和心脏衰老小鼠模型，优化模型评价指标，为抗衰老药物评价提供疾病模型支撑。

方法

（1）快速衰老小鼠模型：小鼠分为模型1组（5 mg/kg，每7 d 1次）、模型2组（8 mg/kg，每10 d 1次）、模型3组（8 mg/kg，每7 d 1次）、模型4组（10 mg/kg，每10 d 1次）和模型5组（10 mg/kg，每7 d 1次），腹腔注射3次，连续观察60 d，记录小鼠的生存率；（2）心脏衰老小鼠模型：小鼠分为对照组、模型-1组（2 mg/kg）、模型-2组（5 mg/kg）、模型-3组（8 mg/kg）和模型-4组（10 mg/kg），每10 d一次，共注射2次，连续造模30 d，结束后使用小动物高频超声成像技术（UBM）评价射血分数（EF）、缩短分数（FS）和最大血流速度；检测血清中肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）、白介素6（IL-6）和白介素1β（IL-1β）的水平；检测心肌组织超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）、琥珀酸脱氢酶（SDH）和过氧化氢酶（CAT）含量；检测心肌组织病理、纤维连接蛋白（FN）、β-半乳糖苷酶染色（β-gal）和p16蛋白等心脏衰老相关指标。

结果

（1）快速衰老小鼠模型：实验期间各个模型组之间小鼠的体质量和存活率均呈显著下降趋势，且随着DOX造模剂量增加和造模间隔时间缩短，体质量和存活率下降愈发明显；（2）心脏衰老小鼠模型：与对照组比较，2、5、8和10 mg/kg DOX可以显著升高LDH含量（P < 0.01），降低GSH-Px活力（P < 0.05或P < 0.01）；5、8和10 mg/kg DOX可以显著降低小鼠体质量（P < 0.01），同时小鼠的EF、FS和最大血流速度均显著降低（P < 0.05或P < 0.01），血清中的IL-6含量显著增加（P < 0.05或P < 0.01），SOD含量显著降低（P < 0.05或P < 0.01），β-半乳糖苷酶和p16蛋白表达显著升高（P < 0.05或P < 0.01），心肌组织出现水样和空泡变性；而8和10 mg/kg DOX还可以显著升高CK-MB水平（P < 0.01）和增加心脏纤维化程度（P < 0.01）；此外，10 mg/kg DOX还可以增加IL-1β和MDA含量（P < 0.01）。

结论

腹腔注射10 mg/kg DOX，每10 d注射一次，共注射3次可以成功建立快速衰老小鼠模型；而腹腔注射5或8 mg/kg DOX，每10 d注射一次，共注射2次可成功建立心脏衰老小鼠模型，引起心功能、心肌酶、炎症、氧化应激、衰老标志物、心脏病理及纤维化的改变，符合心脏衰老的生理病理特点。

关键词

衰老 / 心脏衰老 / 小鼠 / 多柔比星 / 不同剂量

Abstract

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Objective

To establish rapid-aging and cardiac-aging mouse models by intraperitoneal injection of doxorubicin (DOX) at different doses and frequencies, to optimize model-evaluation indices, and provide disease-model support for anti-aging drug evaluation.

Methods

(1) For the rapid-aging model, mice were divided into model 1 (5 mg/kg, once every 7 d), model 2 (8 mg/kg, once every 10 d), model 3 (8 mg/kg, once every 7 d), model 4 (10 mg/kg, once every 10 d), and model 5 (10 mg/kg, once every 7 d) groups. DOX was administered by three intraperitoneal injections and mice were observed continuously for 60 d to record survival rate. (2) For the cardiac-aging model, mice were divided into control, model-1 (2 mg/kg), model-2 (5 mg/kg), model-3 (8 mg/kg), and model-4 (10 mg/kg) groups. Injections were given twice, once every 10 d, for 30 d. After completion, ejection fraction (EF), fractional shortening (FS), and peak blood flow velocity were evaluated by small animal high-frequency ultrasound imaging. Serum levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), interleukin (IL)-6, and IL-1β, and myocardial-tissue levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), succinate dehydrogenase, and catalase were measured. Myocardial tissue pathology, fibronectin, β-galactosidase staining (β-gal), and p16 protein, along with other cardiac aging-related indicators, were assessed.

Results

(1) In the rapid-aging mouse model, body mass and survival rate showed significant downward trends in all modeling groups. Decreases in body mass and survival rate became more pronounced with increasing DOX dose and shortened modeling interval. (2) In the cardiac-aging model, compared with the control group, DOX 2, 5, 8, and 10 mg/kg significantly increased LDH levels (P < 0.01) and decreased GSH-Px activity (P < 0.05 or P < 0.01), and DOX 5, 8, and 10 mg/kg significantly decreased body mass (P <0.01), EF, FS, and peak blood flow velocity (P < 0.05 or P < 0.01). Serum IL-6 levels were significantly increased, SOD content was significantly decreased, and β-galactosidase and p16 protein expression levels were significantly elevated (P < 0.05 or P < 0.01). Myocardial tissue showed hydropic and vacuolar degeneration. DOX 8 and 10 mg/kg also significantly increased CK-MB levels and cardiac fibrosis, and DOX 10 mg/kg increased IL-1β and MDA contents (P < 0.01).

Conclusions

Intraperitoneal injection of DOX 10 mg/kg once every 10 d for three injections successfully established a rapid-aging mouse model, while intraperitoneal injection of DOX 5 or 8 mg/kg once every 10 d for two injections successfully established a cardiac-aging mouse model, which induced changes in cardiac function, myocardial enzymes, inflammation, oxidative stress, aging markers, cardiac pathology, and fibrosis consistent with physiological and pathological characteristics of cardiac aging.

Key words

aging / cardiac aging / mice / doxorubicin / different doses

引用本文

颜宏, 龚吕东, 钟承志, 资志达, 李婷, 吴德松, 郭琰. 不同剂量多柔比星诱导衰老小鼠模型的构建. 中国实验动物学报, 2026 , 34 (3) : 371 -381 . DOI: 10.3969/j.issn.1005-4847.2026.03.006

Hong YAN, Lyudong GONG, Chengzhi ZHONG, Zhida ZI, Ting LI, Desong WU, Yan GUO. Construction of an aging mouse model induced by different doses of doxorubicin[J]. Acta Laboratorium Animalis Scientia Sinica, 2026 , 34 (3) : 371 -381 . DOI: 10.3969/j.issn.1005-4847.2026.03.006

基金

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云南省重点研发计划项目(202203AC100008)
云南省基础研究专项(202401AT070155)

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2026年第34卷第3期

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文章信息

doi: 10.3969/j.issn.1005-4847.2026.03.006

接收时间：2025-09-03
首发时间：2026-08-08
出版时间：2026-03-30

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出版历史

收稿日期：2025-09-03

基金

Key Research and Development Project of Yunnan Province(202203AC100008)

云南省重点研发计划项目(202203AC100008)

Yunnan Fundamental Research Projects(202401AT070155)

云南省基础研究专项(202401AT070155)

作者信息

^1．云南白药集团股份有限公司，昆明　650500

^2．云南省药物研究所，昆明　650111

^3．云南省中药和民族药新药创制企业重点实验室，昆明　650111

通讯作者:

郭琰，男，博士，正高级工程师，研究方向：中药、民族药药效活性研究和新药研发。Email：yaoxueguoyan@126.com

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https://castjournals.cast.org.cn/joweb/zgsydwxb/CN/10.3969/j.issn.1005-4847.2026.03.006

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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