银屑Ⅰ号对咪喹莫特诱导BALB/c小鼠银屑病模型的干预作用  

Antipsoriatic Effects of PsoriasisⅠon Imiquimod-induced Psoriasis-like Dermatitis in BALB/c Mice

作　　者：杭怡宁 黎锦添 王金华 谢玉彬 李秋怿 钟欣欣 查旭山[2] HANG Yi-ning;LAI KAM Tim;WANG Jin-hua;XIE Yu-bin;LI Qiu-yi;ZHONG Xin-xin;CHA Xu-shan(First Clinical Medicine College,Guangzhou University of Chinese Medicine,Guangzhou,510405;Department of Dermatology,First Affiliated Hospital,Guangzhou University of Chinese Medicine,Guangzhou,510405)

机构地区：[1]广州中医药大学第一临床医学院,广州510405 [2]广州中医药大学第一附属医院皮肤科,广州510405

出　　处：《中国中西医结合杂志》2020年第4期453-458,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金面上项目(No.81573980);广东省科技厅项目(No.2017A020215058)。

摘　　要：目的观察银屑Ⅰ号对咪喹莫特(IMQ)诱导的BALB/c小鼠银屑病模型局部皮损及外周血的干预作用。方法 SPF级BALB/c小鼠30只,随机分为对照组、模型组、银屑Ⅰ号高、中、低剂量组,每组6只,除对照组外,其余各组每日外涂62.5 mg 5%IMQ诱导银屑病样动物模型,银屑Ⅰ号高、中、低剂量组小鼠造模期间同时灌胃相应剂量银屑Ⅰ号,共7日。分别观察小鼠背部皮损厚度变化、皮损面积和疾病严重程度指数(PASI),光镜下观察局部皮损组织病理变化,对局部皮损组织依次使用反转录聚合酶链式反应(qPCR)、免疫印迹(Western Blot)法检测维生素D受体(VDR)、血管内皮生长因子(VEGF)在mRNA及蛋白水平表达,采用ELISA法检测外周血白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)含量。结果与对照组比较,模型组小鼠背部皮损皮肤显著增厚,并出现典型银屑病表现,PASI评分随时间推移显著上升;与模型组比较,银屑Ⅰ号各组小鼠背部皮损红斑及鳞屑相对较少、浸润程度较轻,造模区域皮肤厚度及PASI评分与剂量梯度成反比。光镜下模型组小鼠背部皮损表皮全层增厚,呈典型银屑病病理改变;与模型组比较,银屑Ⅰ号高剂量组病理改变最轻,中剂量组次之,低剂量组与模型组比较,差异无统计学意义(P>0.05)。与对照组比较,模型组VDR mRNA及蛋白表达降低(P<0.01,P<0.05),VEGF mRNA及蛋白表达及外周血中IL-6、TNF-α、IFN-γ含量显著升高(P<0.01);与模型组比较,银屑Ⅰ号中、高剂量组VDR mRNA及蛋白表达升高(P<0.05,P<0.01),VEGF mRNA、蛋白表达及外周血IL-6、TNF-α、IFN-γ含量均显著降低(P<0.01),低剂量组VEGF mRNA及蛋白表达均显著降低(P<0.01),外周血中IL-6含量有所降低(P<0.05),VDR mRNA及蛋白表达、TNF-α、IFN-γ含量差异无统计学意义(P>0.05)。结论一定剂量的银屑Ⅰ号可通过抑制异常新生血管形成及炎症环境改善IMQ诱导银屑病小鼠模Objective To observe the anti-psoriatic effects of Psoriasis Ⅰ(PⅠ) on imiquimod(IMO)-induced psoriasis-like dermatitis in BALB/c mice. Methods Thirty SPF grade BALB/c mice were randomly divided into 5 groups: control group, model group, high, middle, and low dose PⅠ groups, 6 in each group. Psoriasis-like dermatitis was induced on the shaved dorsal skin of BALB/c mice(except the control group) by external application of 62.5 mg 5% IMQ. Corresponding doses PⅠ were administrated to mice in the three PⅠ groups by gastrogavage for 7 successive days. The changes of back skin lesion thickness, lesion area, Psoriasis Area and Severity Index(PASI) were respectively evaluated. Histopathological changes were observed under light microscope. The levels of mRNA and protein expressions of vitamin D receptor(VDR) and vascular endothelin growth factor(VEGF) were detected by qPCR and Western Blot. Contents of IL-6, tumor necrosis factor α(TNF-α), and IFN-γ were detected by ELISA. Results Compared with the control group, the skin of the back skin of the model group was significantly thickened with typical manifestations of psoriasis. The PASI score increased significantly as time went by. Compared with the model group, the erythema and scales were relatively less, and the degree of infiltration was milder in each PⅠ group. The skin thickness and PASI score of the model area were inversely proportional to the dose gradient. Results of light microscope showed that the epidermis of the model group was thickened in line with typical pathological changes of psoriasis. Compared with the model group, the pathological changes of high dose PⅠ group were the lightest, followed by middle dose PⅠ group. There were no significant differences between the low dose PⅠ group and the model group(P>0.05). Compared with the control group, mRNA and protein expressions of VDR decreased(P<0.01, P<0.05), the VEGF mRNA and protein of expression, contents of IL-6, TNF-α, and IFN-γ in the peripheral blood significantly increased in t

关 键 词：银屑Ⅰ号 维生素D受体 银屑病动物模型 新生血管 炎症因子 

分 类 号：R285.5[医药卫生—中药学]