基于STAT3/Survivin信号通路研究银屑平丸调控中性粒细胞外诱捕网对银屑病样小鼠的影响*

作者：张玉凤1，席建元2，王 琦1，谢汶芳2，祁 林2，羊 羡2，陈邦第2，李小鹏2

单位：1.湖南中医药大学，湖南 长沙 410208； 2.湖南中医药大学第一附属医院，湖南 长沙 410007

引用：引用：张玉凤，席建元，王琦，谢汶芳，祁林，羊羡，陈邦第，李小鹏.基于STAT3/Survivin信号通路研究银屑平丸调控中性粒细胞外诱捕网对银屑病样小鼠的影响[J].中医药导报,2025, 31(10):1-7.

DOI：10.13862/j.cn43-1446/r.2025.10.001

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摘要：

目的：基于信号转导与转录激活因子3（STAT3）/生存素（Survivin）信号通路研究银屑平丸通过调节中性粒细胞外诱捕网（NETs）对银屑病样（Ps）小鼠的改善作用及其机制。方法：将48只小鼠随机分成6组：空白组、对照组、阿维A组、银屑平丸高剂量组、银屑平丸中剂量组及银屑平丸低剂量组，每组8只。每日在小鼠背部脱毛区域外涂咪喹莫特乳膏（IMQ）以建立银屑病样皮损，同时分别给予相应的药物灌胃干预，连续给药7 d。实验期间每天记录小鼠背部皮损变化，采用银屑病皮损面积和严重程度指数（PASI）进行量化评估；取皮损组织进行HE染色观察组织病理学改变；采用免疫荧光染色检测瓜氨酸化组蛋白H3（Cit-H3）的表达；通过蛋白质印迹法（Western blotting）检测STAT3、p-STAT3和Survivin蛋白的表达水平；运用酶联免疫吸附试验（ELISA）测定血清中髓过氧化物酶（MPO）、中性粒细胞弹性蛋白酶（NE）和NETs的含量。结果：与空白组比较，对照组小鼠背部皮肤呈现出显著的银屑病样改变，如表皮角化不全、棘层厚度减少、真皮乳头水肿伴微血管扩张充血等典型特征；而阿维A组及不同剂量银屑平丸干预组病理损伤程度均有所缓解；相较于空白组，造模后的对照组、阿维A组及不同剂量银屑平丸干预组小鼠PASI评分均显著升高（P<0.01）。同时皮损中的Cit-H3、p-STAT3、Survivin及血清中MPO、NE、NETs水平均显著上调（P<0.01）；与对照组比较，阿维A组及银屑平丸各剂量组小鼠PASI评分均降低，且上述各指标表达水平明显下调（P<0.05），但各组STAT3表达水平差异无统计学意义（P>0.05）。结论：银屑平丸可显著改善Ps小鼠模型的皮损症状，其治疗作用可能与抑制NETs生成有关。此外，STAT3/Survivin信号通路的激活可能参与了银屑病的发病过程。

关键词：银屑病；银屑平丸；中性粒细胞外诱捕网；STAT3/Survivin信号通路；小鼠

Abstract：

Objective: To investigate the therapeutic effects and mechanisms of Yinxieping Wan on psoriasis (Ps) in mice by regulating neutrophil extracellular traps (NETs) through the STAT3/Survivin signaling pathway. Methods: Totally 48 mice were randomly allocated into six groups, including blank group, control group, acitretin group, high-dose Yinxieping Wan group, medium--dose Yinxieping Wan group, and low-dose Yinxieping Wan group, 8 mice in each group. Psoriasis-like skin lesions were induced by daily topical application of imiquimod (IMQ) cream on depilated dorsal skin for 7 consecutive days, with simultaneous intragastric administration of corresponding treatments. Dorsal lesions were daily evaluated using the Psoriasis Area and Severity Index (PASI). Skin lesions were collected for hematoxylin-eosin (HE) staining to assess histopathological changes. Citrullinated histone H3 (Cit-H3) expression was detected by immunofluorescence staining. Western blotting measured STAT3, p-STAT3 and Survivin protein levels. Serum myeloperoxidase (MPO), neutrophil elastase (NE) and NETs concentrations were quantified via enzyme-linked immunosorbent assay (ELISA). Results: Compared with the blank group, the control group exhibited significant psoriasis-like features including parakeratosis, reduced epidermal thickness, dermal papillary edema, and dilated/congested capillaries. Pathological damage was alleviated in acitretin group, high-dose Yinxieping Wan group, medium-dose Yinxieping Wan group, and low-dose Yinxieping Wan group. PASI scores significantly increased in control group, acitretin group, high--dose Yinxieping Wan group, medium-dose Yinxieping Wan group, and low-dose Yinxieping Wan group versus blank group (P<0.01). Lesional Cit-H3, p-STAT3 and Survivin expression, along with serum MPO, NE, and NETs levels, were markedly elevated in model mice (P<0.01). Compared with the control group, acitretin group, high-dose Yinxieping Wan group, medium-dose Yinxieping Wan group, and low-dose Yinxieping Wan group showed reduced PASI scores and downregulated expression of all measured biomarkers (P<0.05), though STAT3 levels remained unchanged across groups (P>0.05). Conclusion: Yinxieping Wan can ameliorate psoriatic skin lesions in mice, potentially by inhibiting NETs formation. Activation of the STAT3/Survivin signaling pathway may contribute to psoriasis pathogenesis.

Key words：psoriasis; Yinxieping Wan; neutrophil extracellular traps; STAT3/Survivin signaling pathway; mice

发布时间：2026-01-08

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