large animal psoriasis model，SD rat imiquimod-induced psoriasis model，Th17-skewed cutaneous inflammation，anti-psoriatic drug pharmacological evaluation

The SD rat imiquimod cream-induced psoriasis model is a gold-standard large rodent psoriasis model based on TLR7/8 innate immune activation and targeted IL-23/Th17 inflammatory axis. It compensates for the shortcomings of mouse models such as limited skin area, insufficient sample collection and narrow dosage gradient for topical administration, and is widely used for in-depth psoriasis mechanism research, topical preparation efficacy evaluation and translational medicine verification. As a specific small-molecule agonist of TLR7/8, imiquimod (IMQ) continuously stimulates SD rat dorsal skin, activates keratinocytes, dendritic cells and innate immune cells, promotes the massive secretion of upstream pro-inflammatory factors such as IL-23 and IL-6, induces CD4+ T cell polarization towards Th17 cells, and triggers the cascading release of inflammatory mediators including IL-17A, IL-22 and TNF-α, resulting in persistent cutaneous immune inflammatory damage. SD rats have thick skin tissue, large lesion area, stable inflammatory phenotypes and high macroscopic lesion recognition. The model stably recapitulates typical clinical psoriasis vulgaris features, including erythema, silvery scaling, epidermal hypertrophy and abnormal keratinization. Pathological manifestations contain hyperkeratosis, parakeratosis, acanthosis, elongated rete ridges, superficial dermal vasodilation, inflammatory cell infiltration and characteristic Munro microabscesses. Compared with mouse models, the SD rat psoriasis model presents a wider inflammatory gradient and sufficient tissue samples, which is more suitable for dose-effect studies and in-depth local mechanism exploration of topical creams, gels and membranes, serving as a core standardized model for dermatological large animal pharmacodynamic evaluation.

SPF-grade SD rats aged 6–8 weeks with a body weight of 180–220 g were used, and male rats were preferred. SD rats have strong vitality, high skin tolerance and stable immune responses to exogenous IMQ stimulation, with uniform psoriasis lesion progression, minor individual differences and extremely low modeling mortality. The rats have broad skin area and sufficient tissue thickness, which can meet the experimental requirements of multi-point sampling, parallel multi-index detection and gradient administration of topical preparations. All rats were housed in an SPF barrier system with constant temperature and humidity, 12 h light/dark cycle, and ad libitum access to food and water. Formal modeling was initiated after 7 days of adaptive sterile feeding. Environmental stress, dust stimulation and exogenous allergen interference were strictly controlled throughout the experiment to ensure consistent immune status and synchronous lesion progression among all groups.

Modeling Success Criteria

Macroscopic Simplified PASI Score

The evaluation system includes four dimensions: erythema, scaling, skin thickening and infiltration degree, with each item scored from 0 to 4 points and a total score ranging from 0 to 16 points. Score 0 represents normal skin, and score 4 represents the most severe single symptom. Rats in the model group presented typical psoriatic signs on dorsal skin, including persistent erythema, stacked silvery white scaling, skin hypertrophy and dermal infiltrative edema. The total lesion score was extremely significantly higher than that of the blank group with statistically significant differences, confirming successful modeling.

Quantitative Skin Thickness Index

The thickness of the central dorsal lesion skin was measured at fixed sites with a high-precision electronic vernier caliper under unified measurement pressure and angle. The skin thickness of the model group was significantly higher than that of the blank group, showing abnormal epidermal hyperplasia and dermal inflammatory edema thickening, which was completely consistent with the core phenotypic characteristics of clinical psoriatic skin hypertrophy.

Histopathological Characteristics

HE staining of rat lesion tissues showed complete typical pathological structures of psoriasis: extensive epidermal hyperkeratosis and parakeratosis, characteristic Munro microabscesses in the stratum corneum, significant acanthosis and regularly elongated epidermal rete ridges. The superficial dermis presented extensive vasodilation, congestion and obvious tissue edema, with diffuse infiltration of a large number of lymphocytes, neutrophils and monocytes. The degree of inflammatory pathological damage was significantly higher than that of the blank group, which was highly consistent with the pathology of human psoriasis vulgaris.

Core Immunoinflammatory Indexes

The expression levels of TLR7/8 downstream and IL-23/Th17 axis core inflammatory factors (IL-17A, IL-22, IL-23, TNF-α, IL-6) in skin tissues and serum of the model group were significantly upregulated, with persistent abnormal activation of the Th17 immune inflammatory pathway and typical immune imbalance characteristics, which served as the core immunological gold standard for confirming the successful construction of the SD rat psoriasis model.

Model Advantages

As a gold-standard large rodent psoriasis model exclusive to SD rats, it makes up for the shortcomings of mouse models such as insufficient tissue volume, thin skin and inapplicability to topical preparation dose-gradient experiments. Rats have large lesion area, wide inflammatory phenotype gradient, intuitive signs, smaller data errors and excellent reproducibility. The modeling mechanism is strictly consistent with the core TLR7/IL-23/Th17 pathogenesis pathway of clinical psoriasis. It achieves rapid modeling within 7 days with no surgical trauma, stable animal status and extremely low mortality. It can meet the requirements of multi-point sampling, parallel multi-index verification and in-depth research on local skin micro-mechanisms, and is highly suitable for preclinical efficacy and translational research of topical traditional Chinese medicine preparations, creams, gels and novel skin drug delivery systems, serving as a high-quality standardized model for high-score SCI papers, project applications and master and doctoral dissertations.

Research Applications

The SD rat imiquimod cream-induced psoriasis model is mainly used for the research of psoriasis immune mechanism, TLR7/8 innate immune activation, IL-23/Th17 inflammatory axis imbalance regulation, abnormal skin keratin proliferation and barrier damage mechanism in large rodents. It is specially applied to the dose-effect, local penetration and efficacy verification of topical preparations with anti-inflammatory, anti-scaling, anti-erythema, anti-epidermal hyperplasia and skin barrier repair effects. It is suitable for preclinical translational research of traditional Chinese medicine compounds, natural active ingredients, novel skin drug delivery preparations and chemical anti-inflammatory drugs, serving as an essential core standard model for large-scale psoriasis animal experiments, new drug development and project conclusion.