psoriasis animal model，propranolol-induced psoriasis model，cutaneous keratinocyte hyperplasia，psoriatic inflammation SD rat model，anti-psoriatic drug screening platform

The SD rat propranolol cream-induced psoriasis model is a classic standardized SCI animal model based on β-adrenergic receptor blockade for simulating clinical drug-induced psoriatic lesions. Different from traditional IMQ immune agonist modeling, it focuses on the disorder mechanism of nerve-immunity-epidermal proliferation and highly recapitulates the pathological characteristics of clinical drug-induced and stress-related psoriasis vulgaris. Propranolol is a non-selective β1/β2 adrenergic receptor antagonist. Continuous topical cutaneous application specifically blocks the cutaneous β-receptor signaling pathway, disrupts skin sympathetic nerve homeostasis, and induces local skin immune microenvironment imbalance. This intervention significantly activates abnormal keratinocyte proliferation, inhibits normal epidermal differentiation, synchronously triggers the activation of skin innate immune cells, and promotes the release of pro-inflammatory factors such as TNF-α, IL-6 and IL-17A, breaking skin immune tolerance and eventually stably forming typical psoriatic lesions including erythema, dry scaling, skin hypertrophy and abnormal keratinization. Pathologically, it recapitulates core clinical psoriasis features: epidermal hyperkeratosis, parakeratosis, acanthosis, elongated rete ridges, superficial dermal inflammatory cell infiltration and vascular proliferation and dilation. SD rats have large skin area, thick epidermis and stable response to topical β-blockers, with mild and uniform lesion progression and minor individual differences, which perfectly compensates for the defects of mild lesions and insufficient sampling volume in mouse models. It is specifically suitable for the research of psoriasis neuroimmune regulation mechanism, abnormal keratin proliferation mechanism, drug-induced psoriasis pathogenesis, and preclinical pharmacodynamic evaluation of anti-psoriatic candidates, serving as the gold-standard model for psoriasis research in the field of neuroimmunology.

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 skin tolerance and stable neuroimmune regulation system, and are highly sensitive to propranolol-mediated β-receptor blockade injury. After modeling, the psoriasiform lesion phenotype is stable and progressive without spontaneous self-healing, with extremely low intra-group individual differences, which is superior to small rodents. Rats have thick skin tissue and highly controllable lesion areas, which can meet the experimental requirements of multi-point sampling, continuous pathological sectioning, multi-dimensional molecular detection and gradient intervention of topical drugs. 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, noise stimulation and temperature and humidity fluctuations were strictly controlled throughout the experiment to avoid interference of exogenous factors on neuroimmune homeostasis and ensure unified modeling conditions 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 dry infiltration, with each item scored from 0 to 4 points and a total score ranging from 0 to 16 points. Score 0 indicates completely normal skin, and score 4 indicates severe single symptom. After modeling, rats in the model group presented typical psoriasiform signs on dorsal skin: persistent light red to bright red erythema, stacked dry white scales, skin hypertrophy and rough dry epidermal infiltration. 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 with a high-precision electronic vernier caliper at fixed detection sites 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 proliferation and thickening as well as mild dermal inflammatory edema, which conforms to the core macroscopic phenotypic characteristics of psoriatic epidermal hypertrophy.

Histopathological Characteristics

HE staining of lesional tissues showed characteristic psoriasiform pathological changes: epidermal hyperkeratosis, focal parakeratosis, obvious acanthosis and regularly elongated epidermal rete ridges. The superficial dermis presented mild vasodilation and congestion with diffuse infiltration of lymphocytes and a small number of neutrophils, without severe suppurative inflammation. The pathological morphology is highly consistent with mild to moderate clinical psoriasis vulgaris, representing a typical psoriasiform pathological phenotype mediated by neuroimmune disorder.

ore Immunoinflammatory Indexes

The expression levels of core psoriatic inflammatory factors (IL-17A, IL-6, TNF-α, IL-22) in skin tissues and serum of the model group were significantly upregulated, accompanied by abnormal elevation of keratinocyte proliferation markers. The model presents significant characteristics of β-receptor blockade-mediated neuroimmune imbalance and epidermal proliferation disorder, which serves as the core academic gold-standard index for confirming successful construction of the propranolol-induced psoriasis model.

Model Advantages

As a gold-standard psoriasis model exclusive to neuroimmune mechanism research, it is different from the traditional immune-activated IMQ model, accurately simulates the progression of clinical drug-induced and stress-mediated psoriasis, and fills the gap in animal experiments on psoriasis neuroregulatory mechanism. It has an innovative modeling mechanism with high academic recognition, and perfectly fits the clinical pathogenesis characteristics of non-infectious, immune disorder and nerve abnormality-mediated psoriasis. SD rats present mild and stable lesions without acute severe inflammatory outbreak or death, with excellent reproducibility. The gentle lesion progression is suitable for observing the long-term effects of drugs on repairing lesions, inhibiting keratin proliferation and regulating neuroimmune imbalance. Sufficient sampling volume supports in-depth multi-level mechanism research, which is highly suitable for neuroimmune-related projects, traditional Chinese medicine mechanism research, new topical preparation development and high-score SCI paper publication.

Research Applications

The SD rat propranolol cream-induced psoriasis model is corely applied to the research of the **nerve-immunity-epidermis interactive regulatory mechanism** of psoriasis, focusing on the mechanisms of abnormal keratin proliferation, skin immune imbalance and persistent lesions mediated by β-adrenergic receptor pathway disorder. It is specially used to evaluate the pharmacodynamic effects of topical preparations on anti-inflammation, anti-scaling, inhibiting epidermal hyperplasia, regulating neuroimmune homeostasis and repairing psoriasiform lesions. It is widely suitable for preclinical screening and mechanism verification of traditional Chinese medicine compounds, natural active ingredients, novel skin drug delivery preparations and neuromodulatory small-molecule drugs, serving as an exclusive essential standardized model for psoriasis neuroimmunology and chronic mild lesion repair research.