文献类型：期刊文献

中文题名：桃红四物汤调控MAPK/NF-κB信号通路治疗大鼠银屑病的作用机理

英文题名：Mechanism of Taohong Siwu Decoction Regulating MAPK/NF-κB Signaling Pathway in the Treatment of Psoriasis in Rats

作者：牛凡琪[1];李炳男[2];何世烨[1];王思农[1];李怡霏[1];周文丽[3];金彩云[1]

第一作者：牛凡琪

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]郑州卫生健康职业学院,河南郑州450000;[3]甘肃中医药大学附属医院,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2025

卷号：39

期号：1

起止页码：17

中文期刊名：中国皮肤性病学杂志

外文期刊名：The Chinese Journal of Dermatovenereology

收录：;北大核心:【北大核心2023】；

基金：国家重点研发计划“中医药现代化研究”重点专项(2018YFC1705302);甘肃省高等学校科技成果转化项目(2017D-17);甘肃省高校教师创新基金项目(2023A-079)。

语种：中文

中文关键词：桃红四物汤;大鼠银屑病模型;MAPK/NF-κB信号通路;银屑病;作用机理

外文关键词：Taohong Siwu Decoction;Rat psoriasis model;MAPK/NF-κB signaling pathway;Psoriasis;Mechanism

摘要：目的 探讨桃红四物汤对大鼠银屑病模型丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)/核转录因子-κB(nuclear factor kappa-B,NF-κB)信号通路相关因子、蛋白及基因表达的干预作用机理。方法 将72只SD大鼠随机分为空白组、模型组、桃红四物汤低、中、高剂量组、阳性对照药物组,采用大鼠背部涂抹5%咪喹莫特乳膏的方法诱导大鼠银屑病样皮损模型,造模同时给予药物干预。给药后对大鼠背部皮损进行银屑病面积和严重程度指数(PASI)评分;HE染色观察皮损组织病理改变进行Baker评分;酶联免疫吸附测定法(ELISA)检测大鼠外周血中白细胞介素(IL)-1β、IL-4、IL-6、IL-36、肿瘤坏死因子(TNF)-α水平;Western blot检测大鼠皮损组织中p38 MAPK、磷酸化(p)-p38 MAPK、细胞外信号调节激酶1/2(ERK1/2)、NF-κB抑制蛋白(IκB)、NF-κB、p-NF-κB蛋白表达水平;Real-time PCR检测大鼠皮损组织中p38 MAPK、ERK1/2、IκB、NF-κB mRNA表达水平;激光共聚焦检测大鼠皮损组织中p38 MAPK、IκB蛋白表达。结果 与空白组比较,模型组大鼠皮损PASI评分、Baker评分和外周血中IL-1β、IL-4、IL-6、IL-36、TNF-α水平升高明显,皮损组织中p38 MAPK、ERK1/2、NF-κB mRNA及蛋白表达水平升高明显,p-p38 MAPK、p-NF-κB蛋白表达水平升高明显,IκB mRNA及蛋白表达水平降低明显(P<0.05);与模型组比较,各给药组大鼠皮损PASI评分、Baker评分和外周血中IL-1β、IL-4、IL-6、IL-36、TNF-α水平降低明显,皮损组织中p38 MAPK、ERK1/2、NF-κB mRNA及蛋白表达水平降低明显,p-p38 MAPK、p-NF-κB蛋白表达水平降低明显,IκB mRNA及蛋白表达水平升高明显(P<0.05)。结论 桃红四物汤可以明显降低大鼠银屑病模型外周血中IL-1β、IL-4、IL-6、IL-36、TNF-α水平及皮损组织中p38 MAPK、p-p38 MAPK、ERK1/2、NF-κB、p-NF-κB表达,升高皮损组织中IκB表达,减轻炎性细胞浸润和表皮增厚程度,通过调控MAPK/NF-κB信号通路,起到治疗银屑病的作用。
Objective To investigate the interventional mechanism of Taohong Siwu Decoction on mitogen-activated protein kinase(MAPK)/nuclear factor kappa-B(NF-κB)signaling pathway-related factors,proteins and genes expression in rat psoriasis models.Methods Seventy-two SD rats were randomly divided into blank group,model group,low-,medium-and high-dose Taohong Siwu Decoction groups,and positive control group.The rat psoriasis-like skin lesion model was induced by applying 5 imiquimod cream on the back of the rats,and simultaneously the modeling was given drug interventions.The psoriasis area and severity index(PASI)was scored by taking photographs,and the histopathological changes of the skin lesions were observed by HE staining for Baker′s score.The levels of interleukin(IL)-1β,IL-4,IL-6,IL-36,and tumor necrosis factor(TNF)-αwere measured in the peripheral blood of rats by ELISA.Western blot was used to detect p38 MAPK,phosphorylated(p)-p38 MAPK,extracellular signal-regulated kinase 1/2(ERK1/2),NF-κB inhibitory protein(IκB),NF-κB,and p-NF-κB in rat skin lesion tissues.Real-time fluorescence quantitative polymerase chain reaction(PCR)was used to detect the expression levels of p38 MAPK,ERK1/2,IκB,and NF-κB mRNA in rat skin lesion tissues,and laser confocal detection was used to detect the expression of p38 MAPK and IκB proteins in rat skin lesion tissues.Results Compared with the blank group,the PASI score,Baker score in rat skin lesion tissues and the levels of IL-1β,IL-4,IL-6,IL-36 and TNF-αin peripheral blood of rats in the model group increased significantly;the expression levels of p38 MAPK,ERK1/2,NF-κB mRNA and protein in rat skin lesion tissues were significantly increased,and the expression levels of p-p38 MAPK and p-NF-κB protein were significantly increased,while the expression levels of IκB mRNA and protein were significantly decreased(P<0.05).Compared with the model group,the PASI score,Baker score in rat skin lesion tissues and the levels of IL-1β,IL-4,IL-6,IL-36 and TNF-αin peripheral blood of rats in each treatment group decreased significantly;the expression levels of p38 MAPK,ERK1/2,NF-κB mRNA and protein in skin lesion tissues decreased significantly,and the expression levels of p-p38 MAPK and p-NF-κB protein decreased significantly,while the expression levels of IκB mRNA and protein increased significantly(P<0.05).Conclusion By regulating the MAPK/NF-κB signaling pathway,Taohong Siwu Decoction can significantly decrease the levels of IL-1β,IL-4,IL-6,IL-36,and TNF-αin the peripheral blood of the rat psoriasis model and the expression of p38 MAPK,p-p38 MAPK,ERK1/2,NF-κB,and p-NF-κB in the skin lesion tissues,increase the expression of IκB in the skin lesion tissues,and reduce the degree of inflammatory cell infiltration and epidermal thickening,thus playing a role in the treatment of psoriasis.