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中国临床药理学与治疗学 ›› 2024, Vol. 29 ›› Issue (9): 1011-1018.doi: 10.12092/j.issn.1009-2501.2024.09.006

• 基础研究 • 上一篇    下一篇

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

李彦梅,马超超,牛凡琪,杨鹏斐,王宁,王思农,李廷保   

  1. 甘肃中医药大学,兰州  730000,甘肃
  • 收稿日期:2023-10-25 修回日期:2023-12-07 出版日期:2024-09-26 发布日期:2024-08-21
  • 通讯作者: 杨鹏斐,男,医学硕士,讲师,研究方向:主要从事中医外科学和皮肤性病教学及临床研究工作。 E-mail: 1297463229@qq.com
  • 作者简介:李彦梅,女,在读硕士研究生,研究方向:中医药治疗皮肤病的临床与实验研究。 E-mail: 2364994926@qq.com
  • 基金资助:
    甘肃省青年科技基金(KJTXM-082245);甘肃省自然科学基金(23JRRA1722)

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

LI Yanmei, MA Chaochao, NIU Fanqi, YANG Pengfei, WANG Ning, WANG Sinong, LI Tingbao   

  1. Gansu University of Traditional Chinese Medicine, Lanzhou 730000, Gansu, China
  • Received:2023-10-25 Revised:2023-12-07 Online:2024-09-26 Published:2024-08-21

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(2 500 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。

关键词: 肤痒静凝胶, 慢性湿疹, 大鼠, 模型, JAK1/STAT5信号通路

Abstract:

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: Thirty-six 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.

Key words: Fuyangjing gel, chronic eczema, rat, model, JAK1/STAT5 signaling pathway

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