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  

Paeoniflorin improves psoriasis by modulating neutrophil extracellular traps in a mouse model of psoriasis

作　　者：郭云龙[1] 史文利[1] 赵瑞[1] 莫金雪[1] 贾淑青[1] 李璟蓉[1] 吴江[1] 方锐华[1] GUO Yunlong;SHI Wenli;ZHAO Rui;MO Jinxue;JIA Shuqing;LI Jingrong;WU Jiang;FANG Ruihua(Guangzhou First People′s Hospital,Guangzhou 510180,China)

机构地区：[1]广州市第一人民医院,广东广州510180

出　　处：《皮肤性病诊疗学杂志》2024年第11期727-733,共7页Journal of Diagnosis and Therapy on Dermato-venereology

基　　金：广州市中医药和中西医结合科技项目(2022A0100A)。

摘　　要：目的探讨芍药苷对咪喹莫特银屑病模型小鼠的治疗作用,并初步探讨其作用机制。方法将15只健康BALB/C小鼠随机分成对照组、模型组,以及低、中、高剂量芍药苷治疗组,每组3只。对照组及模型组背部分别外涂凡士林、咪喹莫特药膏,1次/d,生理盐水灌胃,2次/d;低、中、高剂量芍药苷治疗组背部外涂咪喹莫特药膏,1次/d,并分别给予相应剂量芍药苷[75 mg/(kg·d)、150 mg/(kg·d)、300 mg/(kg·d)]灌胃,2次/d。均连续7 d。观察小鼠涂药处皮肤红斑、鳞屑情况。取小鼠背部皮损组织,HE染色观察组织病理及皮损厚度的变化,免疫荧光检测中性粒细胞浸润,RT-PCR检测TNF-α、IL-17 mRNA表达,Western blot检测瓜氨酸化组蛋白3(CitH3)的表达。结果相较于模型组,低、中、高剂量芍药苷治疗组背部涂药区均红斑变淡、鳞屑减少,表皮增厚明显减轻;中性粒细胞浸润减少;细胞因子TNF-α、IL-17的表达下调(均P<0.001);CitH3表达降低(均P<0.05)。IL-17、CitH3的表达在各剂量组间差异有统计学意义(均P<0.05),并呈现一定的剂量依赖性。结论芍药苷能下调银屑病模型小鼠中相关炎症细胞因子的表达,其作用可能是通过调控中性粒细胞胞外诱捕网实现,继而减轻银屑病小鼠炎症反应从而发挥治疗作用。Objective To investigate the effects of paeoniflorin on imiquimod-induced psoriasis 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 area of the skin were observed.The skin biopsies were obtained from the treated area for H&E staining to observe the changes in histopathology and the skin thickness of the lesions,while immunofluorescence was applied to detect neutrophil infiltration.The expression levels of TNF-αand IL-17 mRNA were assessed with RT-PCR.In addition,Western blot was used to assess the expression of citrullinated histone 3(CitH3).Results Compared with the model group,topical treatment with paeoniflorin attenuated multiple changes in the imiquimod-treated skin,including reduced erythema and scaling,decreased epidermal thickness and neutrophil infiltration,down-regulation of TNF-αand 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,paeoniflorin-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.

关 键 词：银屑病 芍药苷 中性粒细胞胞外诱捕网 

分 类 号：R285.5[医药卫生—中药学]