文献类型：期刊文献

中文题名：基于TLR4/MyD88/NF-κB信号通路探讨过敏煎对特应性皮炎小鼠的保护机制

英文题名：Protective mechanism of Guomin decoction against atopic dermatitis in mice based on TLR4/MyD88/NF-κB signaling pathway

作者：许琳琳[1];张豆[1];丁朋涛[2];席晓霞[3,4];杨鹏斐[1];张潇亚[1];李廷保[1]

第一作者：许琳琳

机构：[1]甘肃中医药大学中医临床学院,甘肃兰州730000;[2]驻马店市中医院,河南驻马店463000;[3]甘肃省中医药研究中心,甘肃兰州730000;[4]兰州大学实验室与设备管理处医学实验中心,甘肃兰州730000

第一机构：甘肃中医药大学中医临床学院

年份：2025

卷号：30

期号：12

起止页码：1648

中文期刊名：中国临床药理学与治疗学

外文期刊名：Chinese Journal of Clinical Pharmacology and Therapeutics

收录：;北大核心:【北大核心2023】；

基金：甘肃省自然科学基金项目(23JRRA1722);甘肃省中医药研究中心开放课题资助项目(zyzx-2024-zx08);甘肃省自然科学实验动物专项(23JRRA1169)。

语种：中文

中文关键词：过敏煎;特应性皮炎;Toll样受体4/髓样分化因子88/核转录因子κB信号通路;动物模型

外文关键词：Guomin decoction;atopic dermatitis;Toll-like receptor 4/myeloid differentiation factor 88/nuclear transcription factorκB signaling pathway activity;animal model

摘要：目的:探讨过敏煎对1-氯-2,4-二硝基氯苯(DNCB)诱导的特应性皮炎(AD)小鼠的作用及机制。方法:将50只小鼠采用DNCB诱导建立AD模型,随机分为模型组、盐酸西替利嗪组(1.3 mg/kg)及过敏煎低、中、高剂量组(3.25、6.5、13 g/kg),空白组10只,共60只。各组小鼠灌胃按设定剂量给予相应受试药,连续14 d。观察小鼠皮损情况,进行皮损严重程度评分。治疗结束后计算脾指数;采用苏木精-伊红(HE)染色法观察皮损组织病理形态变化;酶联免疫吸附试验(ELISA)法检测血清中血清免疫球蛋白E(IgE)、白细胞介素6(IL-6)、IL-1β、肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)及转化生长因子β(TGF-β)的含量;实时荧光定量聚合酶链式反应(Real-time PCR)检测小鼠皮损组织中Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核转录因子κB(NF-κB)、NF-κB抑制蛋白α(IκB-α)基因表达;蛋白免疫印迹法(Western Blot)检测皮损组织中TLR4、MyD88、NF-κB p65、p-NF-κB p65蛋白水平。结果:与空白组比较,模型组小鼠的皮损评分升高(P<0.01);表皮过度角化,棘层肥厚,真皮层可见嗜酸性粒细胞等炎性细胞浸润;脾脏指数及血清IgE、IL-6、IL-1β、TNF-ɑ、IFN-γ升高(P<0.01),TGF-β1下降(P<0.01);皮损组织中TLR4、MyD88、NF-κB、NF-κB p65、p-NF-κB p65表达升高,IκB-α表达降低,差异具有统计学意义(P<0.01)。与模型组比较,过敏煎组小鼠的皮损面积缩小,评分降低(P<0.01);表皮过度角化减轻,棘层轻度肥厚,真皮层有少量炎性细胞浸润;脾脏指数及血清IgE、IL-6、IL-1β、TNF-α、IFN-γ降低(P<0.01),TGF-β1升高(P<0.01);皮损组织中TLR4、MyD88、NF-κB、NF-κB p65、p-NF-κB p65表达降低,IκB-α表达升高(P<0.05)。结论:过敏煎可减轻AD小鼠瘙痒症状,降低脾脏指数,减轻皮肤炎症反应。其可能通过TLR信号通路调节炎症反应和转录,抑制NF-κB中p65亚基的激活,影响下游炎症因子的释放以达到治疗作用。
AIM:To investigate the protective effect and mechanism of Guomin decoction on 1-chloro-2,4-dinitrochlorobenzene(DNCB)induced atopic dermatitis(AD)in mice.METHODS:Fifty mice were induced by DNCB to establish atopic dermatitis model,and were randomly divided into model group,Cetirizine hydrochloride group(1.3 mg/kg),Guomin decoction low,medium and high-dose groups(3.25,6.5,13 g/kg),and blank group 10 mice,60 mice in total.Each group of mice was given the corresponding test drug according to the set dose by intragastric administration for 14 consecutive days.The skin lesions were observed and the severity of skin lesions were scored.The organ index was calculated after treatment.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of skin lesions.Serum immunoglobulin E(Ig-E),interleukin-6(IL-6),IL-1β,tumor necrosis factor alpha(TNF-ɑ),interferon gamma(IFN-γ)and transforming growth factorβ(TGF-β)were detected by enzyme-linked immunosorbent assay(ELISA).Real-time fluorescence quantitative polymerase chain reaction(Real-Time)the gene expression of toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),nuclear transcription factorκB(NF-κB),NF-κB inhibitory proteinα(IκB-α)were detected by PCR.The expression levels of TLR4,MyD88,NF-κBp65 and p-NF-κBp65 in skin lesions were detected by Western Blot.RESULTS:Compared with blank group,the lesion score of mice in model group was increased(P<0.01).The epidermis was hyperkeratosis,the spinous layer was hypertrophic,and eosinophils and other inflammatory cells infiltrated the dermis.Spleen index and serum IgE,IL-6,IL-1β,TNF-alpha and IFN-γwere increased(P<0.01),while TGF-β1 was decreased(P<0.01).The expressions of TLR4,MyD88,NF-κB,NF-κBp65 and P-NF-κBP65 were increased,while the expressions of IκB-αwere decreased,with statistical significance(P<0.01).Compared with the model group,the skin area of mice in the allergic decoction group was reduced and the score was decreased(P<0.01).The epidermal hyperkeratosis was alleviated,the spinous layer was slightly hypertrophic,and there was a small amount of inflammatory cell infiltration in the dermis.Spleen index and serum IgE,IL-6,IL-1β,TNF-alpha and IFN-γwere decreased(P<0.01),while TGF-β1 was increased(P<0.01).The expressions of TLR4,MyD88,NF-κB,NF-κBp65 and PNF-κBP65 were decreased,while the expressions of IκB-αwere increased(P<0.05).CONCLUSION:Guomin decoction can relieve pruritus,spleen index and skin inflammation in AD mice.It may regulate inflammatory response and transcription through TLR signaling pathway,inhibit the activation of p65 subunit in NF-κB,and affect the release of downstream inflammatory factors to achieve therapeutic effects.