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·kg^(-1)·d^(-1))、模型+HDG高剂量(50 mg·kg^(-1)·d^(-1))和模型+卤米松阳性对照组(每组8只小鼠)。给药7 d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m RNA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Mincle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Mincle/Syk/NF-κB信号途径相关。
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-αin 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.
作者
何馨雨
钟霞
刘鹏
谭睿陟
HE Xinyu;ZHONG Xia;LIU Peng;TAN Ruizhi(Southwest Medical University,Luzhou 646000,Sichuan,China;Research Center of Integrated Traditional Chinese and Western Medicine,Affiliated Traditional Medicine Hospital,Southwest Medical University,Luzhou 646000,Sichuan,China;Beijing Traditional Chinese Medicine Hospital Shunyi Hospital,Shunyi 101300,Beijing,China)
出处
《中国临床药理学与治疗学》
CAS
CSCD
2023年第12期1339-1346,共8页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
四川省自然科学基金资助项目(2022NSFSC0606)。
