Slit2在小鼠银屑病样皮炎模型炎性浸润中的作用  

Effects of Slit2 on inflammatory infiltration in mouse model of imiquimod-induced psoriasis

作　　者：熊莉 吴倩 郑云婷 黄珂 顾玉洁 周春丽 李元朝 王儒鹏 XIONG Li;WU Qian;ZHENG Yunting;HUANG Ke;GU Yujie;ZHOU Chunli;LI Yuanchao;WANG Rupeng(Department of Dermatology and Rheumatology Immunology,Xinqiao Hospital,Army Medical University,Chongqing 400037,China)

机构地区：[1]陆军军医大学新桥医院皮肤风湿免疫科,重庆400037

出　　处：《免疫学杂志》2023年第4期277-286,共10页Immunological Journal

基　　金：国家自然科学基金(82003338)。

摘　　要：目的观察分泌型糖蛋白Slit2在咪喹莫特诱导的小鼠银屑病样皮炎模型中的表达及作用。方法采用免疫荧光观察咪喹莫特诱导的小鼠银屑病样皮损中Slit2的定位,PCR及Western blot检测皮损中Slit2的表达。30只小鼠随机分为5组:正常组、IMQ模型组、Slit2 siRNA组、Slit2蛋白低剂量组(100 ng/ml)、Slit2蛋白高剂量组(300 ng/ml),每组6只小鼠。每天对小鼠皮肤进行PASI评分,HE染色测量表皮厚度,计数各组真皮内炎症细胞数及血管密度,RT-PCR检测各组皮损处IL-23、IL-17A、IL-22 mRNA表达量,免疫组化检测各组皮损处Ki67表达及CD3 T细胞数量。结果咪喹莫特诱导的小鼠银屑病样皮炎模型皮损处Slit2的表达升高。相较于模型组,Slit2 siRNA处理后PASI评分增加,表皮变厚、表皮细胞增殖程度增加,真皮炎性细胞浸润增多及血管密度升高,IL-23、IL-17A、IL-22 mRNA水平升高,CD3 T细胞数量明显增加。给予重组Slit2蛋白处理后,PASI评分降低,表皮变薄,表皮细胞增殖程度降低,真皮炎性细胞浸润及血管密度降低,IL-23、IL-17A、IL-22 mRNA水平降低,CD3 T细胞浸润明显减少。结论Slit2在咪喹莫特诱导的小鼠银屑病样皮损中表达升高,使用Slit2 siRNA抑制皮损处Slit2表达可加重皮炎程度,在皮损处使用重组Slit2蛋白处理可减轻皮炎程度,Slit2对咪喹莫特诱导的小鼠银屑病样皮炎具一定的抗炎作用。This study was designed to investigate the expression and role of secretory glycoprotein Slit2 in a mouse model of imiquimod(IMQ)-induced psoriasis.Total of 30 mice were randomly divided into 5 groups,including control group,IMQ model group,Slit2 siRNA group,Slit2 protein low-dose group(100 ng/ml)and highdose group(300 ng/ml),with 6 mice in each group.Immunofluorescence was applied to locate the Slit2 in mice with imiquimod-induced psoriasis-like lesions;PCR and Western blot was employed to detect the expression level of Slit2 in lesions.The PASI score was evaluated every day.HE staining was used to observe the epidermal thickness and count the number of inflammatory cells and vessel density in the dermis;RT-PCR was used to detect the mRNA expression levels of IL-23,IL-22 and IL-17A;Immunohistochemistry was used to detect the expression of Ki67 in epidermis and the number of CD3 T cells.Data showed that the expression of Slit2 in mouse psoriasis-like lesions were increased.Compared with the IMQ group,Slit2 siRNA treatment increased the levels of PASI score,epidermal thickness,inflammatory cells infiltration and vessel density in dermis,the degree of epidermal proliferation,the number of CD3 T cells,and the expression of IL-23,IL-22 and IL-17A mRNA.While compared with IMQ group,the Slit2 protein treatment group demonstrated great alleviation in the symptoms mentioned above.Taken together,Slit2 is highly expressed in psoriasis-like lesions,and Slit2 silence can aggravate the severity of psoriasis-like lesions,while recombinant Slit2 protein treatment can alleviate psoriasis-like lesions.Slit2 has certain anti-inflammatory effects on imiquimod-induced psoriasis-like dermatitis in mice.

关 键 词：Slit2蛋白 Slit2 siRNA 银屑病 咪喹莫特 炎性浸润 

分 类 号：R758.63[医药卫生—皮肤病学与性病学]