蜈蚣败毒饮对银屑病模型鼠外周血中滤泡辅助性T细胞及其主导通路影响的机制研究  

Research on the mechanism of Wugong Baidu Decoction on the Tfh cell and its dominant pathway in the peripheral blood of psoriasis model mice

作　　者：任宇坤 张琼 张晴[2] 林丽 杨素清[2] 安月鹏[2] REN Yukun;ZHANG Qiong;ZHANG Qing;LIN Li;YANG Suqing;AN Yuepeng(Heilongjiang University of Chinese Medicine,Harbin 150040,China;First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学,哈尔滨150040 [2]黑龙江中医药大学附属第一医院,哈尔滨150040

出　　处：《长春中医药大学学报》2022年第8期867-872,共6页Journal of Changchun University of Chinese Medicine

基　　金：国家自然科学基金项目(81904201,81973846);国家重点研发计划“中医药现代化研究”重点专项课题(2018YFC1705301);黑龙江省博士后资助经费项目(LBH-Z20198);黑龙江省普通本科高等学校青年创新人才培养计划项目(UNPYSCT-2020229)。

摘　　要：目的研究中药制剂蜈蚣败毒饮对银屑病模型鼠外周血中滤泡辅助性T细胞(follicular helper T cell,Tfh)的影响,并检测Tfh通路中关键刺激、转录、分泌因子的变化情况,结合银屑病模型鼠的皮损指数评估,分析皮损与Tfh细胞及其主导通路之间的相关性。方法将30只小鼠随机分为6组,分别为空白组、模型组、西药组、低剂量组、中剂量组、高剂量组。经咪喹莫特诱导建模,于药液灌胃前后采用鼠银屑病皮损面积和严重程度指数(mice psoriasis area and severity index,MPASI)评分法评价皮损指数,并计算其变化量(△MPASI);灌胃后采用流式细胞法检测外周血中标记CD4+CXCR5+的Tfh细胞数,采用ELISA法检测Tfh细胞主导通路中刺激因子(IL-6、IL-21)、转录因子(Bcl-6、STAT3)、分泌因子(CXCR5、ICOS、PD-1、CD40L)的血清含量;并采用线性回归分析法,整体评价各药物组小鼠△MPASI与Tfh通路各指标间的相关性。结果在皮损疗效方面,各药物组均能够改善银屑病模型鼠的皮损指数(P<0.05或P<0.01),以西药组和高剂量组的作用最为显著(P<0.01),中药各剂量组呈现出一定的量效依赖关系;在细胞表达方面,银屑病模型鼠外周血中Tfh的细胞数显著高于空白组小鼠(P<0.01),西药组和高剂量组小鼠Tfh细胞数显著减低(P<0.01),中药各剂量组对Tfh细胞均有显著的调控作用(P<0.01);在血清因子含量方面,Tfh主导通路在银屑病模型鼠中表现出异常表达的趋势(P<0.05或P<0.01),西药组和高剂量组能够显著下调IL-6、IL-21、Bcl-6、STAT3、CXCR5、ICOS、CD40L(P<0.01),上调PD-1(P<0.01);在相关性分析方面,△MPASI与Tfh细胞数及其通路中的关键因子均具有相关性(P<0.05),其中与PD-1呈正相关,与其余关键因子呈负相关。结论蜈蚣败毒饮可能通过调控Tfh细胞的表达及其主导通路中上下游因子的链锁式反应,发挥治疗银屑病的作用。Objective To study the effect of the TCM preparation Wugong Baidu Decoctio on the follicular helper T cell(Tfh)in the peripheral blood of psoriasis model mice,and to detect the changes of the key stimulation,transcription and secretion factors in the Tfh pathway,to analyze the correlations between skin lesions,the Tfh cell and its dominant pathway based on the evaluation of the skin lesion indexes in psoriasis model mice.Methods A total of thirty mice were randomly divided into 6 groups,namely a blank group,a model group,a western medicine group,a low-dose group,a middle-dose group and a high-dose group.After the model was induced by imiquimod,the skin lesion indexes were evaluated by the scoring method of mice psoriasis area and severity index(MPASI)before and after an intragastric administration,and the changes(△MPASI)were calculated,while after an intragastric administration,the number of the Tfh cell labeled with CD4+CXCR5+in the peripheral blood was detected by the flow cytometry,and the serum contents of stimulation factors(IL-6 and IL-21),transcription factors(Bcl-6 and STAT3)and secretion factors(CXCR5,ICOS,PD-1 and CD40L)in the dominant pathway of the Tfh cell were detected by ELISA.The correlation between△MPASI and indicators of the Tfh pathway of the mice in each drug group was evaluated as a whole by the linear regression analysis.Results In terms of the skin lesion efficacy,the skin lesion indexes of psoriasis model mice were improved in each drug group(P<0.05 or P<0.01),while the effect of the western medicine group and the high-dose group was the most significant(P<0.01),and the traditional Chinese medicine groups showed a certain dose-effect dependence.In terms of the cell expression,the number of the Tfh cell in the peripheral blood of the psoriasis model mice was significantly higher than that of the blank group mice(P<0.01),while the number of the Tfh cell in the western medicine group and the high-dose group was decreased significantly(P<0.01),and the traditional Chinese medicine groups ha

关 键 词：银屑病 蜈蚣败毒饮 滤泡辅助性T细胞 趋化因子受体 可诱导共刺激分子 程序性死亡受体 

分 类 号：R275.9[医药卫生—中西医结合]