促炎和抗炎细胞因子及VEGF在AEW诱发的干皮症痒模型小鼠脊髓水平的表达

Expression Changes of Pro-and Anti-inflammatory Cytokines and VEGFs in Spinal Cord of Mice with Dry Skin Pruritus Induced by AEW

目的利用已建立的丙酮/二乙醚溶液和水造成小鼠干皮症模型(AEW模型),在C57BL/6小鼠身上诱发慢性痒,检测促炎症细胞因子、抗炎症细胞因子及血管内皮细胞生长因子(VEGF)在颈段脊髓的表达,并探讨它们在AEW诱发的干皮症慢性痒发病机制中的作用。方法外用丙酮/二乙醚混合液(1∶1)和水7天建立C57BL/6小鼠的AEW模型,观察小鼠搔抓行为学,定量PCR分析促炎症细胞因子白细胞介素IL-1β、IL-6、IL-12a、IL-18和肿瘤坏死因子TNF-α,抗炎症细胞因子IL-4、IL-11和IL-13,以及VEGF-a、VEGF-b和VEGF-c在颈部脊髓的mRNA表达水平变化。结果与对照组相比,AEW模型组小鼠的自发性搔抓次数明显多于对照组;促炎症因子IL-1β、IL-6、IL-12a和TNF-αmRNA在脊髓表达升高,而抗炎症因子IL-11和IL-13 mRNA在脊髓表达则显著降低,三种VEGF中,只有VEGF-a在脊髓表达显著增加。结论在干皮症慢性痒模型鼠的脊髓,促炎症因子和VEGF-a表达显著增加,抗炎症因子表达显著降低,针对这些因子及其受体的干预手段可为临床治疗提供新思路。

Objective To investigate the expression of pro- and anti-inflammatory cytokines and vascular endothelial growth factor（VEGFs）in the cervical spinal cord of dry skin disease model（AEW model）mice and the possible role in the pathogenesis of chronic itch.Methods AEW model of C57BL/6 mice were established by using acetone/diethyl ether mixture（1：1）and water for 7 days.The behavior of mice were observed.Quantitative PCR was used to analyze the expression of proinflammatory cytokine including IL-1β, IL-6, IL-12a and TNF-α, anti-inflammatory cytokines including IL-4, IL-11 and IL-13, and three kinds of vascular growth factor VEGF-a, VEGF-b and VEGF-c from cervical spinal cord tissues.Results Compared with the control group, the number of spontaneous scratching in the AEW mice was significantly increased.In the cervical spinal cord of AEW mice, the IL-1β, IL-6, IL-12a, IL-18 and TNF-α mRNA levels were significantly increased, the IL-11 and IL-13 mRNA levels were significantly decreased, and among the three VEGFs only the VEGF-a mRNA level was significantly increased.Conclusion A variety of inflammatory cytokines and growth factors are associated with mechanisms of chronic central（spinal）itch, and the interventions for these factors and/or their receptors would provide a new approach for clinical treatment.