芍药苷通过调控中性粒细胞胞外诱捕网在银屑病模型小鼠中发挥治疗作用OA

Objective To investigate the effects of paeoniflorin on imiquimod-induced psoria-sis in a mouse model and the underlying mechanisms.Methods Fifteen healthy BALB/C mice were randomly divided into the control,model,and model group-treated with low-,medium-,and high-doses of paeoniflorin,once daily for 7 days.The back skin of mice in the control and model groups were treated topically with Vaseline and imiquimod ointment,respectively.The imiquimod-treated mice were intragastrically given either saline or paeoniflorin at doses of 75 mg/(kg·d),150 mg/(kg·d)and 300 mg/(kg·d),twice daily.The erythema and scaling on the treated ar-ea of the skin were observed.The skin biopsies were obtained from the treated area for H&E stai-ning to observe the changes in histopathology and the skin thickness of the lesions,while immuno-fluorescence was applied to detect neutrophil infiltration.The expression levels of TNF-α and IL-17 mRNA were assessed with RT-PCR.In addition,Western blot was used to assess the expres-sion of citrullinated histone 3(CitH3).Results Compared with the model group,topical treat-ment with paeoniflorin attenuated multiple changes in the imiquimod-treated skin,including re-duced erythema and scaling,decreased epidermal thickness and neutrophil infiltration,down-reg-ulation of TNF-α and IL-17 mRNA expression(P＜0.001 vs.imiquimod alone for all)in addition to reduction in expression levels of CitH3(all P＜0.05 vs.imiquimod alone).Moreover,paeoni-florin-induced changes in expression levels of IL-17 and CitH3 were dose-dependent(P＜0.05 for both).Conclusion Paeoniflorin can modulate neutrophil extracellular traps,resulting in down-regulation of the expression levels of inflammatory cytokines,consequently alleviating cutaneous inflammation in a mouse model of psoriasis.