基于JAK1/STAT5信号通路探讨肤痒静凝胶治疗慢性湿疹作用机制  

Mechanism of Fuyangjing gel in the treatment of chronic eczema via JAK1/STAT5 signaling pathway

作　　者：李彦梅 马超超 牛凡琪 杨鹏斐[1] 王宁[1] 王思农[1] 李廷保[1] LI Yanmei;MA Chaochao;NIU Fanqi;YANG Pengfei;WANG Ning;WANG Sinong;LI Tingbao(Gansu University of Traditional Chinese Medicine,Lanzhou 730000,Gansu,China)

机构地区：[1]甘肃中医药大学,甘肃兰州730000

出　　处：《中国临床药理学与治疗学》2024年第9期1011-1018,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：甘肃省青年科技基金(KJTXM-082245);甘肃省自然科学基金(23JRRA1722)。

摘　　要：目的:探讨肤痒静凝胶对慢性湿疹大鼠模型蛋白酪氨酸激酶1(janus protein kinase 1,JAK1)/信号转导与转录激活子5(signal transducerand activator of transcription 5,STAT5)信号通路调控作用的分子机制。方法:将36只SPF级Wistar大鼠随机分为正常组、模型组、青鹏软膏组(2500 mg·kg^(-1)·d^(-1))、肤痒静凝胶低(0.08 g/g)、中(0.16 g/g)、高(0.32 g/g)剂量组。除正常组外,其余组大鼠均采用2,4-二硝基氯苯丙酮液背部诱导慢性湿疹样病变。造模3周后青鹏软膏组及肤痒静凝胶低、中、高剂量组分别涂抹相应药物治疗;模型组涂抹空白凝胶基质,每日1次,共2周,正常组不做处理。观察慢性湿疹大鼠背部皮损的严重程度和病理变化;Western blot法检测大鼠背部皮肤组织中磷酸化蛋白酪氨酸激酶1(p-JAK1)和磷酸化信号转导与转录激活子5(p-STAT5)蛋白表达;qRT-PCR法检测大鼠背部皮肤组织中胸腺基质淋巴细胞生成素(thymic stromallymphopietin,TSLP)、JAK1、STAT5、白细胞介素-10(IL-10)和IL-17 mRNA表达水平;酶联免疫吸附法(ELISA)测定大鼠血清中IL-4、IL-6、IL-10、IL-13和IL-17水平。结果:与正常组比较,模型组大鼠血清中IL-4、IL-6、IL-13和IL-17水平明显升高,IL-10水平明显降低(P<0.05),背部皮损组织中p-JAK1、p-STAT5蛋白和TSLP、JAK1、STAT5、IL-17 mRNA表达水平明显升高,IL-10 mRNA水平明显降低(P<0.05)。与模型组比较,青鹏软膏组、肤痒静凝胶低、中、高剂量组大鼠血清中IL-4、IL-6、IL-13和IL-17水平明显降低,IL-10水平明显升高(P<0.05),背部皮损组织中p-JAK1、p-STAT5蛋白和TSLP、JAK1、STAT5、IL-17 mRNA表达水平明显降低,IL-10 mRNA水平明显升高(P<0.05)。与肤痒静凝胶低、中剂量组比较,青鹏软膏组大鼠血清中IL-4、IL-6、IL-13和IL-17水平明显降低,IL-10水平明显升高(P<0.05),背部皮损组织中p-JAK1、p-STAT5蛋白和TSLP、JAK1、STAT5、IL-17 mRNA表达水平明显降低,IL-10 mRNA水平明AIM:To explore the molecular mechanism of Fuyangjing gel in the treatment of chronic eczema rats model based on janus protein kinase 1(JAK1)/signal transducer and activator of transcription 5(STAT5)signaling pathway.METHODS:Thirtysix SPF Wistar rats were randomly divided into normal group,model group,Qingpeng ointment group,Fuyangjing gel low,medium and high dose groups.Except the normal group,the other groups of rats were treated with 2,4-dinitrochlorophenone solution to induce chronic eczema-like lesions on the back.After 3 weeks of modeling,Qingpeng ointment group and Fuyangjing gel low,medium and high dose groups were respectively treated with corresponding drugs.The model group was smeared with blank gel matrix once a day for 2 weeks,while the normal group was not treated.The severity and pathological changes of back lesions in chronic eczema rats were observed.The expression of phosphorylated protein tyrosine kinase 1(p-JAK1)and phosphorylated signal transduction and transcriptional activator 5(p-STAT5)in rat dorsal skin was detected by Western blot.Detection of thymic stromallymphopietin(TSLP),JAK1,STAT5,interleukin-10(IL-10)and IL-17 mRNA expression levels in rat back skin by qRT-PCR;The levels of IL-4,IL-6,IL-10,IL-13 and IL-17 in serum of rats were determined by enzyme-linked immunosorbent assay(ELISA).RESULTS:Compared with normal group,the serum levels of IL-4,IL-6,IL-13 and IL-17 in model group were significantly increased,while IL-10 levels were significantly decreased(P<0.05).The expression levels of p-JAK1,p-STAT5 protein and TSLP,JAK1,STAT5 and IL-17 mRNA in back lesions were significantly increased,while IL-10 mRNA levels were significantly decreased(P<0.05).Compared with model group,serum levels of IL-4,IL-6,IL-13 and IL-17 in Qingpeng ointment group and Fuyangjing gel low,medium and high dose groups were significantly decreased,while IL-10 levels were significantly increased(P<0.05).The expression levels of p-JAK1,p-STAT5 protein and TSLP,JAK1,STAT5 and IL-17 mRNA in back lesions were significa

关 键 词：肤痒静凝胶 慢性湿疹 大鼠 模型 JAK1/STAT5信号通路 

分 类 号：R965.2[医药卫生—药理学]