盐酸普萘洛尔诱导豚鼠耳部银屑病模型的建立与验证

doi:10.12300/j.issn.1674-5817.2026.011

摘要/Abstract

摘要：

目的采用5%盐酸普萘洛尔乳剂诱导豚鼠耳部银屑病，建立一种稳定的局部银屑病动物模型，并验证其在药效评价中的应用价值。方法 29只6~8周龄的普通级雄性Hartley豚鼠，按体重随机分组，筛选9只豚鼠作为正常组，其余动物为造模组，造模组涂抹5%盐酸普萘洛尔乳剂于右耳背部，每日4次，连续4天，以耳厚度差>0.05 mm及银屑病样皮损面积和疾病严重程度指数（PASI）评分>3分为成模标准；成模动物以右耳耳厚度差值为主指标，以PASI评分、体重为副指标均衡随机分组，分为模型组、1.6 mg/kg 甲氨蝶呤组，连续给药10 d。试验期间观察皮损、体重、耳厚度差值及PASI评分变化，末期取材检测耳重量、脾脏指数、耳组织病理变化以及肥大细胞浸润程度指标。结果造模组动物造模2 d即出现红肿以及增厚的银屑病样皮损现象，并伴有明显搔抓行为，于4~9 d为模型的高峰期，耳部皮肤显著红肿、增厚、鳞屑增多；模型组的PASI评分、耳厚度差值、耳肿胀、脾脏指数、组织病理变化以及肥大细胞浸润均显著高于正常组；甲氨蝶呤均能显著改善上述检测指标。结论成功建立了一种稳定、可重复的盐酸普萘洛尔诱导豚鼠耳部银屑病模型，适用于局部银屑病的药效作用评价。

关键词: 银屑病, 豚鼠, 盐酸普萘洛尔, 动物模型, 药效评价

Abstract:

Objective To induce psoriasis in the ears of guinea pigs using 5% propranolol hydrochloride emulsion, establish a stable local psoriasis animal model, and verify its application value in drug efficacy evaluation. Methods Twenty-nine 6-8 week-old male Hartley guinea pigs of normal strain were randomly grouped according to their body weight. Nine guinea pigs were selected as the control group, and the remaining animals were the model group. The model group was treated with 5% propranolol hydrochloride emulsion on the right ear back, 4 times a day for 4 consecutive days. The criteria for model formation were an ear thickness difference > 0.05 mm and a Psoriasis-like skin lesion area and disease severity index (PASI) score > 3. The model animals were evenly and randomly grouped based on the ear thickness difference as the main indicator, and with PASI score and body weight as secondary indicators, into the model group, the 1.6 mg/kg methotrexate group, and were given continuous treatment for 10 days. During the experiment, changes in skin lesions, body weight, ear thickness difference, and PASI score were observed. At the end of the experiment, samples were taken for detection of ear weight, spleen index, ear tissue pathological changes, and mast cell infiltration degree indicators. Results The animals in the modeling group showed redness, swelling, and thickening of psoriasis-like skin lesions on the right ear 2 day after modeling, accompanied by obvious scratching behavior. The peak period was 4-9 days. The ear skin was significantly red, thick, and had more scales. The PASI score, ear thickness difference, ear swelling, spleen index, tissue pathological changes, and mast cell infiltration degree indicators of the modeling group were significantly higher than those of the normal group. Methotrexate could significantly improve the above detection indicators. Conclusion This study successfully established a stable and repeatable psoriasis model on the ear of guinea pigs induced by propranolol hydrochloride, which is suitable for the evaluation of the efficacy of local psoriasis.

Key words: Psoriasis, Guinea pig, Propranolol hydrochloride, Animal model, Pharmacological efficacy evaluation

中图分类号:

R-332

蒙飞彪,王林仪,张文强,等.盐酸普萘洛尔诱导豚鼠耳部银屑病模型的建立与验证[J]. 实验动物与比较医学.. DOI: 10.12300/j.issn.1674-5817.2026.011.

MENG Feibiao,WANG Linyi,ZHANG Wenqiang,et al. Establishment and Validation of a Guinea Pig Model of Ear Psoriasis Induced by Propranolol Hydrochloride[J]. Laboratory Animal and Comparative Medicine. DOI: 10.12300/j.issn.1674-5817.2026.011.

图/表 9

表1 5%盐酸普萘洛尔乳剂配方

Table 1 5% Propranolol Hydrochloride Formula

比例 Ratio	组分 Component	重量（g） Weight (g)	百分比（%） Percentage (%)
油相Oil phase	硬脂酸Stearic acid	1.4	14
油相Oil phase	液体石蜡Liquid paraffin	2.4	24
水相Aqueous phase	三乙醇胺Triethanolamine	0.3	3
	甘油Glycerol	0.9	9
	蒸馏水Distilled water	4.5	45
药物Medicine	盐酸普萘洛尔Propranolol hydrochloride	0.5	5
总量Total quantity		10	100

图1 实验流程示意图
注：PRO，盐酸普萘洛尔；MTX，甲氨蝶呤片；SLP，芍苓片；ig，灌胃；PASI，银屑病样皮损面积和疾病严重程度指数评分。

Figure 1 Schematic diagram of the experimental process
Note： PRO， Propranolol hydrochloride； MTX， methotrexate Tablets； SLP， Shaoling tablets； ig， Gavage； PASI， Psoriasis area and severity index.

表2 PASI评分细则

Table 2 PASI Scoring Criteria

皮肤泛红程度 Degree of skin redness	鳞屑 Scale	增厚程度 Degree of thickening	严重程度 Different degrees of severity	转换评分 Conversion score
无泛红现象 No redness at all	耳部表面无可见鳞屑	未见增厚	无症状	0
耳部皮肤呈淡红色 The skin on the ear is a light red color.	部分皮损表面完全或覆有鳞屑，以细微鳞屑为主	略有增厚，但尚属轻微范围	轻度	1
耳部皮肤呈红色 The skin on the ear is red.	大多数皮损表面完全或不完全覆有鳞屑，鳞屑呈片状	呈中等程度增厚，变化较为显著	中度	2
耳部皮肤呈深红色 The skin on the ear is a deep red color	几乎所有皮损表面覆有鳞屑，较厚成层	明显增厚，变化突出	重度	3
耳部皮肤红色极深 The skin on the ear is extremely red	全部皮损表面均覆有鳞屑，鳞屑很厚成层	异常增厚，已达严重程度	极重度	4

表3 病理诊断病变程度判读以及半定量评分标准^[8]

Table 3 Criteria for Pathological Diagnosis, Degree of Lesion, and Semi-quantitative Scoring System

病变程度 Degree of lesion	组织学改变 Histological changes	评分（分） Score(points)
正常Normal	未观察到组织学改变或组织结构基本正常	0
轻微Slight	病理损伤范围零星可见，不构成区域性	0.5
轻度Mild	灶性、多灶性或散在分布的损伤，损伤范围在100倍镜下可见1/3-1个视野	1
中度Moderate	灶性、多灶性或散在分布的损伤，损伤范围在100倍镜下可见1-3个视野	2
重度Severe	灶性、多灶性或散在分布的损伤，损伤范围在100倍镜下可见3个视野以上	3

图2 豚鼠耳部银屑病模型体重变化趋势（ˉn = 9）
注：与模型组比较，ns表示P > 0.05。

Figure 2 Body weight change trend of the guinea pig ear psoriasis model （n = 9）
Note： Compared with the model group， ns indicates P> 0.05.

图3 豚鼠耳部造模部位皮肤观察和PASI评分变化趋势（n = 9）
注：A：分组前豚鼠耳部造模图和PASI评分（正常组 n = 9；造模组 n = 20）；B：分组后豚鼠耳部造模图和PASI评分（n = 9）。与正常组比较，^##P < 0.01，^#P < 0.05；与模型组比较，^**P < 0.01，^*P < 0.05。

Figure 3 Observation of the skin at the ear modeling site in guinea pigs and the trend of PASI score changes（n = 9）
Note： A： Pre-grouping ear modeling diagrams and PASI scores of guinea pigs （control group n = 9； modeling group n = 20）； B： Post-grouping ear modeling diagrams and PASI scores of guinea pigs （n = 9 ）. Compared with the control group，^##P < 0.01， ^#P < 0.05； compared with the model group， ^**P < 0.01， ^*P < 0.05.

图4 豚鼠耳部银屑病模型实验期间耳厚度差变化
注：A：分组前和分组后豚鼠右耳耳厚度差值（正常组 n = 9；造模组 n = 20）；B：分组前和分组后豚鼠左耳耳厚度差值（n = 9）。与正常组比较，^##P < 0.01，^#P < 0.05；与模型组比较，^**P < 0.01，^*P < 0.05，ns表示P > 0.05。

Figure 4 Changes in ear thickness during the experiment of the guinea pig ear psoriasis model
Note： A： Difference in ear thickness of the right ear of guinea pigs before and after grouping （control group n = 9； model group n = 20）； B： Difference in ear thickness of the left ear of guinea pigs before and after grouping （n = 9）. Compared with the control group，^##P < 0.01， ^#P < 0.05； compared with the model group， ^**P < 0.01， ^*P < 0.05， ns indicates P> 0.05.

表4 豚鼠耳部银屑病模型耳肿胀度 (

x ˉ

± s，n=9)

Table 4 The ear swelling of the guinea pig psoriasis model

组别

Groups

左耳片（g）

Left ear（g）

右耳片（g）

Right ear（g）

耳肿胀度（g）

Ear swelling degree (g)

正常组

control group

0.0695±0.004

0.0669±0.0050

0.0004±0.0024

模型组

model group

0.0713±0.002

0.0896±0.0052^##

0.0187±0.0040^##

甲氨蝶呤组

MTX group

0.0702±0.004

0.0826±0.0056*

0.0123±0.0051**

表4 豚鼠耳部银屑病模型耳肿胀度 ( $x ˉ$ ± s，n=9)

Table 4 The ear swelling of the guinea pig psoriasis model

组别

Groups

左耳片（g）

Left ear（g）

右耳片（g）

Right ear（g）

耳肿胀度（g）

Ear swelling degree (g)

正常组

control group

0.0695±0.004

0.0669±0.0050

0.0004±0.0024

模型组

model group

0.0713±0.002

0.0896±0.0052^##

0.0187±0.0040^##

甲氨蝶呤组

MTX group

0.0702±0.004

0.0826±0.0056*

0.0123±0.0051**

图5 豚鼠耳部银屑病模型脾脏指数、耳组织组织病理改变与肥大细胞浸润
注：A：豚鼠脾脏组织图片及脾脏指数统计图；B：耳组织H-E染色视图及病变程度半定量评分统计图；C：耳组织肥大细胞浸润视图及肥大细胞浸润病变程度半定量评分统计图。与正常组比较，^##P < 0.01，^#P < 0.05；与模型组比较，^**P < 0.01，^*P < 0.05。

Figure 5 Spleen index， histopathological changes of ear tissue， and mast cell infiltration in the murine ear psoriasis model
Note： A： Picture of guinea pigs spleen tissue， B： Spleen index of guinea pigs. Compared with the control group，^##P < 0.01， ^#P < 0.05； compared with the model group， ^**P < 0.01， ^*P < 0.05.

参考文献 25

[1]	Geng R S Q, Sibbald R G. Cutaneous psoriasis: clinical aspects and treatments[J]. Adv Skin Wound Care, 2025, 38(4): 176-182. DOI: 10.1097/ASW.0000000000000243 .
[2]	Helm M F, Clebak K T, Critchfield L, et al. Psoriasis and papulosquamous disorders[J]. Prim Care, 2025, 52(3): 567-591. DOI: 10.1016/j.pop.2025.05.007 .
[3]	Chan J J. Psoriasis: an update on topical and systemic therapies[J]. Aust Prescr, 2025, 48(3): 87-92. DOI: 10.18773/austprescr.2025.026 .
[4]	Parab S, Doshi G. The experimental animal models in psoriasis research: a comprehensive review[J]. Int Immunopharmacol, 2023, 117: 109897. DOI: 10.1016/j.intimp.2023.109897 .
[5]	Tatu A L, Elisei A M, Chioncel V, et al. Immunologic adverse reactions of β-blockers and the skin[J]. Exp Ther Med, 2019, 18(2): 955-959. DOI: 10.3892/etm.2019.7504 .
[6]	Kim G K, del Rosso J Q. Drug-provoked psoriasis: is it drug induced or drug aggravated?: understanding pathophysiology and clinical relevance[J]. J Clin Aesthet Dermatol, 2010, 3(1): 32-38.
[7]	张萌萌, 刘树民, 孙慧娟, 等. 盐酸普萘洛尔致银屑病样大鼠模型的剂量、时间及性别探讨[J]. 海南医科大学学报, 2025, 31(5): 351-359, 372. DOI: 10.13210/j.cnki.jhmu.20240830.004 .
	Zhang Mengmeng, Liu Shumin, Sun Huijuan, et al. Exploration of dose, time and sex in a psoriasis-like rat model caused by propranolol hydrochloride[J]. J Hainan Med Univ, 2025, 31(5): 351-359, 372. DOI: 10.13210/j.cnki.jhmu.20240830.004 .
[8]	Shackelford C, Long G, Wolf J, et al. Qualitative and quantitative analysis of nonneoplastic lesions in toxicology studies[J]. Toxicol Pathol, 2002, 30(1): 93-96. DOI: 10.1080/01926230252824761 .
[9]	Tampa M, Mitran M I, Mitran C I, et al. Psoriasis: what is new in markers of disease severity?[J]. Medicina (Kaunas), 2024, 60(2): 337. DOI: 10.3390/medicina60020337 .
[10]	Kshirsagar S J, Adhav P S, Laddha U D, et al. Navigating psoriasis: From immune mechanisms to natural healing approaches[J]. Int Immunopharmacol, 2025, 144: 113626. DOI: 10.1016/j.intimp.2024.113626 .
[11]	李慧贤, 胡丽, 郑焱, 等. 基于全球疾病负担(GBD)大数据的中国银屑病流行病学负担分析[J]. 中国皮肤性病学杂志, 2021, 35(4): 386-392. DOI: 10.13735/j.cjdv.1001-7089.202003197 .
	Li Huixian, Hu Li, Zheng Yan, et al. Analysis of the epidemiological burden of psoriasis in China based on the big data of global burden of disease study (GBD)[J]. Chin J Dermatovenereology, 2021, 35(4): 386-392. DOI: 10.13735/j.cjdv.1001-7089.202003197 .
[12]	Shirley S N, Watson A E, Yusuf N. Pathogenesis of inflammation in skin disease: from molecular mechanisms to pathology[J]. Int J Mol Sci, 2024, 25(18): 10152. DOI: 10.3390/ijms251810152 .
[13]	Lin Z C, Yang S C, Tran T T P, et al. Animal models of psoriasis for novel drug discovery: a literature update[J]. Expert Opin Drug Discov, 2025, 20(9): 1193-1208. DOI: 10.1080/17460441.2025.2528959 .
[14]	Xi Ruofan, Nie Yiwen, Lu Hanzhi, et al. Phytochemicals from Stellera chamaejasme alleviate psoriasis by modulating the immune microenvironment via the JAK2/PI3K/AKT pathway[J]. Int Immunopharmacol, 2025, 165: 115540. DOI: 10.1016/j.intimp.2025.115540 .
[15]	牛凡琪, 李炳男, 何世烨, 等. 桃红四物汤调控MAPK/NF-κB信号通路治疗大鼠银屑病的作用机理[J]. 中国皮肤性病学杂志, 2025, 39(1): 17-29. DOI: 10.13735/j.cjdv.1001-7089.202406010 .
	Niu Fanqi, Li Bingnan, He Shiye, et al. Mechanism of Taohong Siwu decoction regulating MAPK/NF-κB signaling pathway in the treatment of psoriasis in rats[J]. Chin J Dermatovenereology, 2025, 39(1): 17-29. DOI: 10.13735/j.cjdv.1001-7089.202406010 .
[16]	Vinardell M P. Methodological shortcomings in the reports of the imiquimod psoriatic model[J]. Exp Dermatol, 2022, 31(3): 299-303. DOI: 10.1111/exd.14479 .
[17]	李倾, 屠佳妮, 胡佳, 等. 咪喹莫特诱导银屑病动物模型的研究进展[J]. 中国实验动物学报, 2025, 33(8): 1222-1234. DOI: 10.3969/j.issn.1005-4847.2025.08.011 .
	Li Qing, Tu Jiani, Hu Jia, et al. Research progress on animal models of imiquimod-induced psoriasis[J]. Acta Lab Anim Sci Sin, 2025, 33(8): 1222-1234. DOI: 10.3969/j.issn.1005-4847.2025.08.011 .
[18]	Awad V M, Sakhamuru S, Kambampati S, et al. Mechanisms of beta-blocker induced psoriasis, and psoriasis de novo at the cellular level[J]. Cureus, 2020, 12(7): e8964. DOI: 10.7759/cureus.8964 .
[19]	伍长娟, 沈娟. 盐酸普萘洛尔造模周期对豚鼠银屑病模型的影响[J]. 承德医学院学报, 2015, 32(5): 374-376. DOI: CNKI:SUN:CDYX.0.2015-05-004 .
	Wu Changjuan, Shen Juan. Effects of propranolol hydrochloride modeling period on guinea pig models of psoriasis[J]. J Chengde Med Coll, 2015, 32(5): 374-376. DOI: CNKI:SUN:CDYX.0.2015-05-004 .
[20]	Zhao Fang, Wang Yujie, Zuo Haojie, et al. Cyclin-Dependent kinase 9 (CDK9) inhibitor Atuveciclib ameliorates Imiquimod-Induced Psoriasis-Like dermatitis in mice by inhibiting various inflammation factors via STAT3 signaling pathway[J]. Int Immunopharmacol, 2024, 129: 111652. DOI: 10.1016/j.intimp.2024.111652 .
[21]	Sbidian E, Chaimani A, Garcia-Doval I, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis[J]. Cochrane Database Syst Rev, 2022, 5(5): CD011535. DOI: 10.1002/14651858.CD011535.pub5 .
[22]	杨怡冰, 乔媛媛, 李灿哲, 等. 血热证与血瘀证银屑病大鼠模型的建立及证候差异评价[J]. 世界科学技术-中医药现代化, 2025, 27(8): 2360-2372. DOI: 10.11842/wst.20240724001 .
	Yang Yibing, Qiao Yuanyuan, Li Canzhe, et al. Establishment and evaluation of psoriasis rat model with blood-heat syndrome and blood-stasis syndrome[J]. World Sci Technol Mod Tradit Chin Med, 2025, 27(8): 2360-2372. DOI: 10.11842/wst.20240724001 .
[23]	Bai Linkun, Su Yazhen, Ning Zongdi, et al. Challenges and opportunities in animal models of psoriatic arthritis[J]. Inflamm Res, 2023, 72(6): 1291-1301. DOI: 10.1007/s00011-023-01752-w .
[24]	高祥, 刘宁, 葛文萍, 等. 三转基因银屑病小鼠模型建立与表型分析[J]. 中国比较医学杂志, 2015, 25(7): 11-15. DOI: 10.3969/j.issn.1671-7856.2015.07.003 .
	Gao Xiang, Liu Ning, Ge Wenping, et al. Establishment of the psoriasis transgenic mouse model and analysis of the phenotype[J]. Chin J Comp Med, 2015, 25(7): 11-15. DOI: 10.3969/j.issn.1671-7856.2015.07.003 .
[25]	泰刚, 李洋, 杨志敏, 等. 银屑病(血热证)豚鼠复合模型的建立及评价研究[J]. 药物评价研究, 2020, 43(11): 2176-2180. DOI: 10.7501/j.issn.1674-6376.2020.11.005 .
	Tai Gang, Li Yang, Yang Zhimin, et al. Establishment and evaluation of a compound model of psoriasis (blood heat syndrome) in guinea pigs[J]. Drug Eval Res, 2020, 43(11): 2176-2180. DOI: 10.7501/j.issn.1674-6376.2020.11.005 .