常春藤皂苷元通过调控巨噬细胞Mincle介导的炎症减轻银屑病小鼠皮肤损伤的作用机制
Hederagenin improves psoriasis skin lesions by inhibiting macro-phage mincle-mediated inflammation
何馨雨 1钟霞 2刘鹏 3谭睿陟2
作者信息
- 1. 西南医科大学医学检验系,泸州 646000,四川
- 2. 西南医科大学附属中医医院中西医结合研究中心,泸州 646000,四川
- 3. 北京中医医院顺义医院,顺义 101300,北京
- 折叠
摘要
目的:观察常春藤皂苷元(hederagenin,HDG)改善银屑病小鼠皮肤损伤和炎症的作用与机制.方法:通过在C57小鼠背部祛毛并连续涂抹咪喹莫特7 d建立小鼠银屑病动物模型,造模后1 h给予HDG灌胃治疗.总计设置正常组、模型组、模型+HDG低剂量(25 mg·kg1·d-1)、模型+HDG高剂量(50 mg·kg1·d-1)和模型+卤米松阳性对照组(每组8只小鼠).给药7d后,对患处皮肤进行病理检测,以及炎症指标进行ELISA、实时定量PCR检测,Mincle及其下游信号进行免疫组织化学、免疫荧光和Western blot检测.结果:与模型组比较,HDG干预组皮肤病理损伤以及炎性细胞浸润均得到不同程度改善;实时定量PCR和皮肤组织悬液ELISA结果证实HDG干预后小鼠皮肤中炎症因子IL-1β、IL-6和TNF-α的mRNA及蛋白水平均比模型组降低(P＜0.01),说明HDG具有显著抗炎症作用;免疫组织化学和Western blot结果表明,与正常组相比,模型组小鼠皮肤中Min-cle 的蛋白表达量显著增加(P＜0.01),给予HDG干预后明显下调(P＜0.01);免疫荧光证实模型组皮肤中Mincle表达与巨噬细胞标志物F4/80共定位;Western blot实验发现,HDG在治疗组中不仅下调了 Mincle的蛋白表达,同时也下调了 Mincle下游信号Syk和NF-κB的蛋白磷酸化水平.结论:HDG可显著改善银屑病小鼠皮肤损伤和巨噬细胞相关炎症,其潜在分子机制可能与下调Min-cle/Syk/NF-κB信号途径相关.
Abstract
AIM:To observe the effects and mech-anisms of hederagenin(HDG)in improving psoria-sis skin lesions and inflammation in mice.METH-ODS:A mouse model of psoriasis was established by depilation of the back and continuous applica-tion of imiquimod for 7 days in C57 mice.After modeling,HDG was administered orally(low dose:25 mg·kg-1·d-1 and high dose:50 mg·kg-1·d-1)1 hour later,and a positive control group was treated with dexamethasone.After 7 days of drug interven-tion,pathological,immunohistochemical,immuno-fluorescence,ELISA,real-time quantitative PCR,and Western blot analyses were performed on the skin lesions of each group of mice.RESULTS:Com-pared with the model group,the HDG intervention group showed varying degrees of improvement in skin pathological damage and inflammatory cell in-filtration.Real-time PCR and ELISA results of skin tissue suspension confirmed that the mRNA and protein levels of inflammatory factors IL-1β,IL-6,and TNF-α in mouse skin were reduced in the HDG intervention group compared to the model group,indicating a significant anti-inflammatory effect of HDG.Immunohistochemical and Western blot re-sults showed that compared with the normal group,the protein expression of Mincle in the skin of the model group mice was significantly in-creased,which was significantly down-regulated af-ter HDG intervention.Immunofluorescence con-firmed the co-localization of Mincle expression and macrophage marker F4/80 in the skin of the model group.Western blot analysis revealed that HDG not only down-regulated the protein level of Mincle in the treatment group but also reduced the protein phosphorylation levels of downstream signaling molecules Syk and NF-κB.CONCLUSION:Heder-agenin intervention can significantly inhibit patho-logical damage and macrophage-related inflamma-tion in psoriasis,and its potential molecular mecha-nism may be related to the down-regulation of the Mincle/Syk/NF-κB signaling pathway.
关键词
常春藤皂苷元/Mincle/皮肤损伤/炎症/银屑病Key words
hederagenin/mincle/macrophage/inflammation/psoriasis引用本文复制引用
基金项目
四川省自然科学基金资助项目(2022NSFSC0606)
出版年
2023
国家科技期刊平台
NSTL
维普
万方数据