目的：探讨瞬时受体电位（transient receptor potential,TRPV1）-胃泌素释放肽受体（gastrin releasing peptide receptor,GRPR）-JAK1STAT3信号在过敏性接触性皮炎皮肤瘙痒的作用机制。方法：使用方酸二丁酯（dibutyl cubic acid,SADBE）诱导小鼠过敏性接触性皮炎（allergic contact dermatitis,ACD）模型,分为正常组、SADBE组和TRPV1敲除组。检测小鼠皮肤厚度、血清免疫球蛋白E（immunoglobulin E,IgE）;免疫荧光和FISH染色检测抗体角蛋白（KRT14）、TRPV1和GRPR表达,分析其表达与小鼠划痕数的相关性;荧光定量聚合酶链反应（fluorescent quantitative polymerase chain reaction,qPCR）检测ACD模型小鼠脊髓中TRPV1-GRPR-JAK1STAT3信号的表达。结果：SADBE诱导的小鼠ACD模型中,在第3―7天引起了长时间的皮肤瘙痒。小鼠血清IgE水平升高,脾脏重量增加,表皮增厚;小鼠腰椎脊髓切片的双重FISH研究表明TRPV1和GRPR之间存在显着重叠,与正常组比较,SADVE组TRPV1、GRPR、JAK1和STAT3 mRNA表达升高,与SADBE组比较,而TRPV1敲除其表达降低,TRPV1敲除组划痕数、表皮厚度减少,差异有统计学意义（P<0.05）。结论：SADBE诱导的ACD导致小鼠瘙痒增加,而抑制TRPV1-GRPR-JAK1STAT3信号表达可抑制过敏性接触性皮炎皮肤瘙痒。
Abstract
Objective To investigate Transient receptor potential (TRPV1) - Gastrin releasing peptide receptor, GRPR) -JAK1STAT3 signaling mechanism on skin pruritus in allergic contact dermatitis. Methods The allergic contact dermatitis (ACD) model was induced by dibutyl cubic acid (SADBE) in mice, which were divided into normal group, SADBE group and TRPV1 knockout group. Detect skin thickness and serum immunoglobulin E (IgE). Immunofluorescence and FISH staining were used to detect the expression of Keratin (KRT14), TRPV1 and GRPR in antibody cells, analyze the correlation between their expression and the number of scratches in mice, and fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the expression of TRPV1-GRPR-JAK1STAT3 signal in the spinal cord of ACD model mice. Results In the mouse ACD model induced by SADBE, prolonged skin itching was observed between 3 and 7 days. Elevated serum IgE levels, thickened epidermis, and increased spleen weight were observed also. Dual FISH studies of lumbar spinal cord sections in mice showed significant overlap between TRPV1 and GRPR, with increased expression of TRPV1, GRPR, JAK1, and STAT3 mRNA in the SADVE group compared with the normal group and decreased expression in the SADBE group after TRPV1 knockout. The number of scratches and epidermal thickness decreased in TRPV1 knockout group, and the difference was statistically significant (P<0.05). Conclusion ACD induced by SADBE resulted in increased pruritus in mice, while inhibition of TRPV1-GRPR-JAK1STAT3 signaling suppressed allergic contact dermatitis skin pruritus.
关键词
瞬时受体电位（TRPV1） /
胃泌素释放肽受体（GRPR） /
JAK1STAT3 /
过敏性接触性皮炎 /
皮肤瘙痒
Key words
transient receptor potential (TRPV1) /
gastrin releasing peptide receptor (GRPR) /
JAK1STAT3 /
allergic contact dermatitis /
itchy skin
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参考文献
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基金
内蒙古自治区卫生健康科研基金项目（20200159）
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