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神经肽Y及其受体在银屑病慢性瘙痒中的表达特征

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该文旨在研究神经递质神经肽Y(NPY)及其受体在银屑病小鼠的背根神经节(DRG)与脊髓中的表达特征.将8周龄的雄性C57BL/6小鼠随机分为咪喹莫特(IMQ)模型组和空白对照组两组.观察小鼠的行为学变化和皮肤炎症,采用HE染色分析皮肤炎症,甲苯胺蓝染色分析肥大细胞浸润情况.通过实时荧光定量PCR分析DRG中NPY mRNA的表达变化和皮肤中细胞因子的表达变化,并通过RNA原位杂交技术分析Npy1r(NPY受体Y1相应的基因)、Npy2r(NPY受体Y2相应的基因)的表达情况.鞘内注射Y1拮抗剂或Y2拮抗剂后观察小鼠的行为学变化.IMQ造模小鼠的抓挠行为极显著增加.与对照组相比,IMQ模型组小鼠皮肤出现明显的银屑病样炎症性皮肤病变,而肥大细胞数目并无明显变化.在皮肤中,IMQ模型组IL-4与IL-5 mRNA表达水平与对照组相比没有明显改变;TSLP与IL-33表达水平升高.在DRG中,IMQ模型组NPY的mRNA表达水平与对照组相比升高,Npy2r与Nppb在神经元中有明显的共表达.在脊髓中,Npy1r与Grp有部分共表达,Npy1r与Npy2r同时表达在部分神经元中.在鞘内注射Y1拮抗剂或Y2拮抗剂后,IMQ小鼠的抓挠行为显著增加.IMQ可诱使小鼠出现银屑病样皮损并引起瘙痒,NPY在 DRG中表达水平升高,而Npy1r与Npy2r表达在痒觉神经元中,这表明NPY-Y1/Y2轴影响银屑病模型小鼠的瘙痒症状.
Expression Characteristics of Neuropeptide Y and Its Receptors in Psoriatic Chronic Pruritus
This study aims to describe the expression profiles of the neurotransmitter NPY(neuropeptide Y)and its receptors in the DRG(dorsal root ganglion)and spinal cord of a mouse model of psoriasis.Eight-week-old male C57BL/6 mice were randomly divided into two groups:the IMQ(imiquimod)modeling group and the blank control group.Behavioral changes and skin inflammation of mice were observed in mice,Skin pathological changes and mast cell infiltra-tion were analyzed using HE staining and toluidine blue staining,respectively.The mRNA expression of NPY in DRG and the cytokine expression in skin were analyzed by real-time quantitative PCR,and the expression of Npy1r(the gene cor-responding to NPY receptor Y1)and Npy2r(the gene corresponding to NPY receptor Y2)were analyzed by RNA in situ hybridization.Behavioral changes were observed after intrathecal administration of Y1 antagonist or Y2 antagonist.The scratching behavior of IMQ modeled mice was significantly increased.Compared with the control group,the skin of mice in IMQ model group showed obvious psoriasis inflammatory skin lesions,but the number of mast cells did not change sig-nificantly.In skin,the mRNA expression levels of IL-4 and IL-5 in IMQ group did not change significantly compared with control group,while the expression levels of TSLP and IL-33 were increased.In DRG,the mRNA expression level of NPY was elevated in the IMQ modeling group,and Npy2r was significantly co-expressed with Nppb-positive neurons.In the spinal cord,Npy1r was partially co-expressed with Grp,and Npy1r and Npy2r were co-expressed on some neurons.Intra-thecal administration of Y1 antagonist or Y2 antagonist significantly increased scratching behavior of IMQ mice.IMQ can induce psoriatic lesions in mice and cause pruritus.NPY expression level is increased in DRG,while Npy1r and Npy2r are expressed in itch neurons.The NPY-Y1/Y2 axis is involved in pruritus in psoriatic model mice.

psoriasisitchIMQ(imiquimod)NPY(neuropeptide Y)DRG(dorsal root ganglion)NPY receptor

范立民、刘雪婷、倪曼婷、温玉环、农秀雨、吴瑜丹、陶爱林

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广州医科大学附属第二医院,呼吸疾病国家重点实验室变态反应研究室,广东省过敏反应与免疫重点实验室,广州 510260

银屑病 瘙痒 咪喹莫特(IMQ) 神经肽Y(NPY) 背根神经节 NPY受体

国家自然科学基金国家自然科学基金国家自然科学基金广州市科技局市校(院)联合资助(高水平大学)基础研究项目广东省基础与应用基础研究基金广东省普通高等学校创新团队项目广州市科技计划

8237179782171764818712662024A03J09422023A15150124842021KCXTD046202102010045

2024

中国细胞生物学学报
中国科学院上海生命科学研究院,生物化学与细胞生物学研究所,中国细胞生物学学会

中国细胞生物学学报

CSTPCD
影响因子:0.554
ISSN:1674-7666
年,卷(期):2024.46(3)
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