Department of Nitte University Centre for Animal Research and Experimentation (NUCARE), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), NITTE (Deemed to be University), Paneer, Deralakatte, Mangalore, 575 018, India.
Department of Pharmacovigilance, Norwich Clinical Services, Bangalore, India.
J Basic Clin Physiol Pharmacol. 2021 Feb 8;32(5):959-968. doi: 10.1515/jbcpp-2020-0112.
Psoriasis is an autoimmune, inflammatory disease that needs a reliable animal model. Imiquimod (IMQ)-induced psoriasis is a widely used preclinical tool for psoriasis research. However, this model is sensitive to the genetic variation of mice. The present study explores mice's genetic background on disease stability and severity induced by IMQ.
Three distinct strains of mice (Balb/c, C57BL/6, and Swiss albino) were divided into four groups (Vaseline, IMQ, IMQ+Clobetasol, and IMQ+Curcumin). Psoriasis area severity index (PASI) score, ear/back skin thickness, body weight alterations, and histopathological examination were employed to analyze disease severity. The spleen index studied the systemic effect. Strain effect on oxidative stress induced by IMQ was evaluated by estimating antioxidant factors, superoxide dismutase (SOD), catalase, and glutathione (GSH).
IMQ application resulted in increased PASI score, thickness, and alterations in body weight, confirming disease development in all the mice. However, the disease stability/severity between these strains was not identical. Although IMQ application caused splenomegaly, IMQ+curcumin treated C57BL/6 mice demonstrated a synergistic effect of IMQ and curcumin on the spleen resulting in increased splenomegaly. Decreased cellular enzyme activity in SOD, Catalase, and levels of GSH was observed in IMQ challenged mice, indicating the participation of the redox system in the genesis of the disease that was comparable among the strains.
These results indicate the existence of strain-dependent development of the disease. The Swiss model was found to be better in terms of disease severity and stability than other models. Further, a detailed mechanistic study might help to explain the pathological difference between these strains.
银屑病是一种自身免疫性炎症性疾病，需要可靠的动物模型。咪喹莫特（IMQ）诱导的银屑病是一种广泛用于银屑病研究的临床前工具。然而，这种模型对小鼠的遗传变异敏感。本研究探讨了 IMQ 诱导的疾病稳定性和严重程度与小鼠遗传背景的关系。
将三种不同品系的小鼠（Balb/c、C57BL/6 和瑞士白化病）分为四组（凡士林、IMQ、IMQ+氯倍他索和 IMQ+姜黄素）。采用银屑病面积严重程度指数（PASI）评分、耳/背皮肤厚度、体重变化和组织病理学检查来分析疾病严重程度。脾脏指数研究了全身效应。通过评估抗氧化因子、超氧化物歧化酶（SOD）、过氧化氢酶和谷胱甘肽（GSH）来评估 IMQ 诱导的氧化应激对品系的影响。
IMQ 的应用导致 PASI 评分、厚度和体重的增加，证实了所有小鼠的疾病发展。然而，这些菌株之间的疾病稳定性/严重程度并不相同。虽然 IMQ 的应用导致脾肿大，但 IMQ+姜黄素处理的 C57BL/6 小鼠表现出 IMQ 和姜黄素对脾脏的协同作用，导致脾肿大增加。在 IMQ 挑战的小鼠中观察到细胞酶活性 SOD、过氧化氢酶和 GSH 水平降低，表明氧化还原系统参与了疾病的发生，而且这种参与在不同的品系之间是相似的。
这些结果表明疾病的发展存在与品系相关的差异。瑞士模型在疾病严重程度和稳定性方面比其他模型更好。此外，详细的机制研究可能有助于解释这些菌株之间的病理差异。
