中国中西医结合皮肤性病学杂志2026，Vol.25Issue(4)：294-300,7.
皮肤伤害性感觉神经元分布异常驱动表皮角质形成细胞过度增殖的机制研究
Mechanisms of Aberrant Cutaneous Nociceptive Innervation Driving Epidermal Keratinocyte Hyperproliferation
摘要
Abstract
Objective In order to compare the abundance and innervation of nociceptive sensory neurons in lesional neurodermatitis skin versus normal human skin,and to investigate the effects of recombinant calcitonin gene-related peptide(CGRP)neuropeptide on the proliferation of cultured keratinocytes(KCs)and the changes of signaling molecules involved.Methods Lesional skin from five neurodermatitis patients(admitted from January 2024 to January 2025)and normal control skin from five age-and sex-matched plastic surgery margins were collected.Tissue samples(0.5 cm×0.5 cm)were excised,snap-frozen in liquid nitrogen,and stored at-80℃.Samples were divided into a neurodermatitis group and a normal control group.The expression of substance P(SP),CGRP and transient receptor potential vanilloid 1(TRPV1)in lesional skin of neurodermatitis and normal skin was evaluated using double immunofluorescence staining.Human primary KCs were cultured from foreskin tissue and treated with recombinant CGRP neuropeptide or rimegepant(a CGRP receptor antagonist).Western blotting assay was carried out to measure the levels of proliferating cell nuclear antigen(PCNA)and phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK),and phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2).A chronic dermatitis model was established by topical application of dinitrochlorobenzene(DNCB)onto the ear skin of mice,combined with intragastric administration of rimegepant for intervention.Hematoxylin-eosin(HE)staining and Western blotting were used to assess epidermal thickness and PCNA expression level,respectively.Results As compared with normal human skin,neurodermatitis lesions showed a significant increase in the abundance and innervation of SP+,CGRP+and TRPV1+sensory nerve fibers(P<0.05).Meanwhile,the CGRP treatment upregulated PCNA protein expression in cultured KCs and elevated the levels of p-p38 and p-ERK1/2(P<0.05).Animal studies showed that the rimegepant-treated group had a significant reduction in both epidermal thickness and the expression of CGRP and PCNA proteins in skin tissues compared with the DNCB-only group(P<0.05).Conclusion Abnormally increased nociceptive sensory neurons in the skin exacerbate pruritus by releasing neuropeptides such as SP and CGRP,and also stimulate KCs proliferation.The potential of rimegepant in treating or alleviating pruritus and epidermal hyperproliferation in neurodermatitis warrants further clinical investigation.关键词
伤害性感觉神经元/降钙素基因相关肽/细胞增殖/角质形成细胞/神经性皮炎Key words
Nociceptive sensory neurons/Calcitonin gene-related peptide/Cell proliferation/Keratinocytes/Neurodermatitis分类
医药卫生引用本文复制引用
叶楚环,雷铁池..皮肤伤害性感觉神经元分布异常驱动表皮角质形成细胞过度增殖的机制研究[J].中国中西医结合皮肤性病学杂志,2026,25(4):294-300,7.基金项目
国家自然科学基金面上项目(编号:82273513). （编号:82273513）
