Objective: To explore the therapeutic mechanism of maggot for psoriasis-like lesions in mice from the perspective of immune stress and complement activation regulation.
Methods: Thirty-six male C57BL/6 mice were randomly divided into control group, model group, maggot (1.25%, 2.5%, and 5%) groups, and Benvitimod (1%) group. Psoriasis-like lesions were induced by application of imiquimod cream, and the severity of skin lesions was assessed using the modified Psoriasis Area and Severity Index (MPASI) score. Auricular swelling of the mice was observed, and histopathological changes of the skin lesions were examined with HE staining. Scratching behavior of the mice was observed and the spleen index was calculated. Toluidine blue staining was used to detect mast cells in the skin lesions, and serum levels of IgG, IgM, the complements CH50, C1s, C3, C3a, C5 and C5a, and the inflammatory factors IL-23, IL-17A and TNF-α were determined with ELISA.
Results: In mice with imiquimod-induced psoriasis-like skin lesions, treatment with the maggot at the 3 doses significantly decreased MPASI score, alleviated auricular swelling and pathologies in the skin lesions, reduced scratching behaviors, spleen index, and the number of mast cells in the lesions. Treatment with high-dose maggot significantly lowered serum levels of IgG, C1s, C3a, C5a, IL-23, IL-17A and TNF- α and the levels of C1s, C3, C3a, C5 and C5a in the lesion tissue, and increased serum levels of CH50, C3, and C5. The therapeutic effect of maggot showed a dose-effect dependence.
Conclusion: Maggot can alleviate psoriasislike skin lesions in mice by inhibiting immune stress and complement activation.
目的: 研究五谷虫通过免疫应激-补体活化途径治疗C57BL/6银屑病样小鼠的药效学及作用机制。
方法: 取36只SPF级雄性C57BL/6小鼠,随机分为正常组、模型组、五谷虫(1.25%,2.5%,5%剂量)组、本维莫德(1%)组,6只/组,咪喹莫特乳膏涂抹造模。MPASI评分检测小鼠皮损的严重程度;游标卡尺检测小鼠耳廓肿胀厚度;HE染色检测小鼠背部皮肤及右耳组织病理学变化;观察小鼠抓挠行为学;称重计算小鼠脾脏指数;甲苯胺蓝染色检测小鼠背部皮肤组织肥大细胞数量;ELISA法检测免疫应激(IgG、IgM)、补体活化(CH50、C1s、C3、C3a、C5、C5a)、炎症反应(IL-23、IL-17A、TNF-α)相关因子水平。
结果: 与正常组相比,模型组小鼠MPASI评分、耳廓肿胀厚度均升高(P<0.001);背部皮肤及右耳组织病理损伤加重;抓挠行为次数,脾脏指数,肥大细胞数量,血清IgG、C1s、C3a、C5a、IL-23、IL-17A、TNF-α,组织C1s、C3、C3a、C5、C5a水平均升高(P<0.05),血清CH50、C3、C5水平降低(P<0.001),血清IgM水平有升高趋势,但差异无统计学意义。与模型组相比,五谷虫低、中、高剂量组小鼠MPASI评分、耳廓肿胀厚度降低(P<0.05);背部皮肤及右耳组织病理损伤减弱;抓挠行为次数、脾脏指数、肥大细胞数量降低(P<0.01),五谷虫高剂量组血清IgG、C1s、C3a、C5a、IL-23、IL-17A、TNF-α,组织C1s、C3、C3a、C5、C5a水平降低(P<0.05),血清CH50、C3、C5水平升高(P<0.01)。五谷虫疗效呈现剂量-效应依赖关系。
结论: 五谷虫通过调控免疫应激-补体活化途径发挥治疗银屑病作用。
Keywords: complement activation; immune stress; inflammatory response; maggot; psoriasis.