活血解毒方对银屑病小鼠血管增殖以及炎症因子的干预作用  

Effects of blood-activating toxin-removing formula on vascular proliferation and inflammatory factors in mice with psoriasis

作　　者：李宁飞 王燕 赵京霞 底婷婷 张璐 解欣然 李雪[1,2] 蒙玉娇 刘正荣 翟春艳 郭简宁 李萍 Li Ningfei;Wang Yan;Zhao Jingxia;Di Tingting;Zhang Lu;Xie Xinran;Li Xue;Meng Yujiao;Liu Zhengrong;Zhai Chunyan;Guo Jianning;Li Ping(Beijing University of Chinese Medicine, Beijing 100029, China;Beijing Institute of Traditional Chinese Medicine, Beijing Hospitalof Traditional Chinese Medicine, Capital University of Medical Sciences, Beijing 100010, China)

机构地区：[1]北京中医药大学,北京100029 [2]首都医科大学附属北京中医医院北京市中医研究所

出　　处：《北京中医药大学学报》2019年第4期296-303,共8页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(No.81673989);北京市自然科学基金项目(No.7171003)~~

摘　　要：目的观察活血解毒方对咪喹莫特诱导的银屑病样小鼠模型皮损的干预作用,明确解毒类中药在银屑病治疗中的重要性。方法 BALB/c雄性小鼠55只,随机分为正常对照组、模型组、活血解毒方组、活血方组和甲氨蝶呤组,每组11只,采用外涂咪喹莫特诱导皮肤银屑病样模型。甲氨蝶呤(1 mg/kg)、活血解毒方组(35.1 g/kg)及活血方组(26.9 g/kg)分别予以药物灌胃,正常对照组和模型组予以等量纯净水灌胃。于第7天观察小鼠皮损变化情况后进行处死,取皮肤组织进行检测。HE染色光镜下观察皮损组织形态学变化、表皮层厚度;免疫组织化学法检测皮损中增殖细胞核抗原(PCNA)和T淋巴细胞表面标志CD3的表达以及微血管阳性标记物CD31的表达并检测微血管密度(MVD);采用实时PCR技术检测皮损白细胞介素-17(IL-17)和白细胞介素-23(IL-23)mRNA的表达。结果 HE染色结果显示活血解毒方组皮损表皮增生较模型组少,角化不全的细胞明显减少;表皮厚度降低,P<0.001;活血解毒方组PCNA、CD3阳性表达远低于模型组,P<0.001;活血解毒方MVD明显低于模型组,P<0.05;活血解毒方组IL-17、IL-23的mRNA表达水平均低于模型组,P<0.05。结论活血解毒方的活血润肤作用是通过抑制血管增殖,而清热解毒作用则通过调节IL-23/IL-17轴减少Th17相关因子的表达、表皮层角质细胞的增生、真皮层免疫细胞浸润以改善咪喹莫特诱导的小鼠银屑病样皮损改变。Objective To observe the interventional effect of Huoxue Jiedu Fang(Blood-activating Toxin-removing Formula) on skin lesions in psoriasiform mouse model induced by imiquimod, and clarify the importance of detoxification Chinese medicinals in treatment of psoriasis. Methods Male BALB/c mice(n =55) were randomly divided into normal control group, model group, Huoxue Jiedu Fang group(HJF group), Huoxue Fang(Blood-activating Formula) group(HF group) and methotrexate group(MTX group, each n =11). The psoriasiform mouse model was induced by external coating imiquimod. MTX group was orally given MTX(1 mg/kg), HJF group, HJF(35.1 g/kg), HF group, HF(26.9 g/kg), while normal control group and model group, equivalent pure water. All mice were executed on the 7th d for collecting skin tissue samples. The scores of psoriasis area and severity index(PASI) were observed. The histomorphological changes and epidermal layer thickness of skin lesion tissue were observed by using light microscope after HE staining. The expressions of proliferating cell nuclear antigen(PCNA), marker on T-cell(CD3) and positive microvessel marker(CD31), and microvessel density(MVD) were detected by using immunohistochemistry technique. The mRNA expressions of interleukin-17(IL-17) and interleukin-23(IL-23) were detected by using real-time PCR. Results The results of HE staining showed that epidermal proliferation, para-keratosis cells and epidermal thickness decreased in HJF group compared with model group(P<0.001). The positive expressions of PCNA and CD3 were significantly lower in HJF group than those in model group(P<0.001). MVD was significantly lower in HJF group than that in model group(P<0.05). The mRNA expressions of inflammatory factors(IL-17, IL-23) were significantly lower in HJF group than those in HF group(P<0.05). Conclusion Huoxue Jiedu Fang can inhibit blood vessel proliferation, regulate IL-23/IL-17 axis, reduce expressions of Th17-related factors and relive proliferation of epidermal keratinocytes and infiltration of dermis immunoc

关 键 词：银屑病 活血解毒方 血管增殖 炎症因子 小鼠 

分 类 号：R285.5[医药卫生—中药学]