文献类型：期刊文献

中文题名：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

英文题名：Mechanism of Fuyangjing gel in the treatment of chronic eczema via JAK1/STAT5 signaling pathway

作者：李彦梅[1];马超超[1];牛凡琪[1];杨鹏斐[1];王宁[1];王思农[1];李廷保[1]

第一作者：李彦梅

机构：[1]甘肃中医药大学,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2024

卷号：29

期号：9

起止页码：1011

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：CSTPCD;;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

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

语种：中文

中文关键词：肤痒静凝胶;慢性湿疹;大鼠;模型;JAK1/STAT5信号通路

外文关键词：Fuyangjing gel;chronic eczema;rat;model;JAK1/STAT5 signaling pathway

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水平明显升高(P<0.05)。与青鹏软膏组比较,肤痒静凝胶高剂量组大鼠血清中IL-4、IL-6、IL-10、IL-13和IL-17水平无明显差异(P>0.05),背部皮损组织中p-JAK1、p-STAT5蛋白和TSLP、JAK1、STAT5、IL-10、IL-17 mRNA表达水平无明显差异(P>0.05)。结论:肤痒静凝胶可能通过调控JAK1/STAT5信号通路相关炎症因子、蛋白和基因的表达发挥治疗慢性湿疹的作用。
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 significantly decreased,while the mRNA levels of IL-10 were significantly increased(P<0.05).The serum levels of IL-4,IL-6,IL-13 and IL-17 in Qingpeng ointment group were decreased,while IL-10 levels were 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 decreased,while the mRNA levels of IL-10 were increased(P<0.05).Compared with Qingpeng ointment group,there were no significant differences in serum levels of IL-4,IL-6,IL-10,IL-13 and IL-17 in Fuyangjing gel high-dose group(P>0.05).There were no significant differences in the expression levels of p-JAK1,p-STAT5 protein and TSLP,JAK1,STAT5,IL-10 and IL-17 mRNA in back lesions(P>0.05).CONCLUSION:Fuyangjing gel may play a role in the treatment of chronic eczema by regulating the expression of JAK1/STAT5 signaling pathway related inflammatory factors,proteins and genes.