蜈蚣败毒饮对银屑病小鼠滤泡辅助性T细胞上下游因子的干预作用  

Effect of Wugong Baidu Decoction on Upstream and Downstream Factors of Follicular Helper T Cells in Psoriasis Mice

作　　者：王姗姗[1] 林立 杨素清[1] 安月鹏[1] WANG Shanshan;LIN Li;YANG Suqing;AN Yuepeng(The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine,Heilongjiang 150040,China;Heilongjiang University of Traditional Chinese Medicine,Heilongjiang 150040,China)

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

出　　处：《中国皮肤性病学杂志》2024年第5期488-495,共8页The Chinese Journal of Dermatovenereology

基　　金：国家自然科学基金项目(81973846,81904201);黑龙江省自然科学基金项目(LH2019H108)。

摘　　要：目的 观察蜈蚣败毒饮对滤泡辅助性T(Tfh)细胞上、下游因子白细胞介素-6(IL-6)、核转录基因(Bcl-6)、可诱导共刺激分子(ICOS)以及肿瘤坏死因子相关激活蛋白(CD40L)表达的干预,探讨其对银屑病的治疗机制。方法 将C57BL/6小鼠30只随机分6组,每组5只,并依次命名为空白组、模型组、西药对照组、蜈蚣败毒饮低、中、高剂量组。咪喹莫特诱导建立银屑病小鼠模型。建模完成后空白组和模型组小鼠给予生理盐水灌胃,各给药组小鼠药物灌胃处理。评估治疗前后各组小鼠的银屑病皮损面积和严重程度指数(MPASI),观察皮损微观病理改变情况、qRT-PCR法检测IL-6、Bcl-6、ICOS、CD40L mRNA水平,Western blot法测定IL-6、Bcl-6、ICOS、CD40L蛋白含量,最后对皮损检测指标与皮损改善程度进行相关性分析,用以评价皮损与该通路的关联。结果 药物处理后蜈蚣败毒饮各剂量组的小鼠MAPSI分值均出现下降(P<0.01),△MPASI均表现为升高(P<0.01),且蜈蚣败毒饮高剂量组与西药对照组表现相当,差异无统计学意义(P>0.05);皮损HE染色结果显示蜈蚣败毒饮不同浓度组都表现出对银屑病样皮损的正向干预作用,且高剂量组更加明显;蜈蚣败毒饮低、中、高三个剂量组和西药对照组小鼠皮损中IL-6、Bcl-6、ICOS、CD40L mRNA的表达量均明显降低,(P<0.01);蜈蚣败毒饮不同浓度组小鼠IL-6、Bcl-6、ICOS、CD40L的蛋白含量表达量均下调(P<0.01、P<0.05);相关性分析结果显示,小鼠△MPASI与IL-6、Bcl-6、ICOS、CD40L的mRNA表达和蛋白含量均表现出负相关性(P<0.01)。结论 蜈蚣败毒饮可能通过对IL-6和Bcl-6的负向干预而抑制Tfh细胞的上游通路,下调ICOS和CD40L的表达而抑制Tfh细胞的下游通路,进而影响Tfh细胞的分化和功能发挥,表现出对银屑病样皮损的改善,发挥对银屑病的治疗作用。Objective To observe the effects of Wugong Baidu decoction(WGBDY) on the expression of follicular helper T cell upstream and downstream factors,including interleukin-6(IL-6),nuclear transcription gene(Bcl-6),inducible costimulatory molecule(ICOS) and tumor necrosis factor-related activation intervention of protein(CD40L).Methods Thirty C57BL/6 mice were randomly divided into 6 groups:blank group,model group,western control group,WGBDY low,medium and high-dose groups,with 5 mice in each group.After the mouse model of psoriasis was established using quimod,the mice in the blank and model group were intragastrically administered with physiological saline,and the mice in each administration group were intragastrically treated with drugs.The mouse psoriasis area and severity index(MPASI) was evaluated.The pathological changes of the skin lesions were observed.IL-6,Bcl-6,ICOS,CD40L mRNA and protein levels were detected by qRT-PCR and Western blot respectively.Finally,a correlation analysis was conducted between the skin lesion detection indicators and the degree of skin lesion improvement.Results After drug treatment,MAPSI scores of mice in each dose group were decreased(P<0.01),△MPASI scores were increased(P<0.01),and the performance of WGBDY high-dose group was similar to that of western control group,with no significant difference(P>0.05).The results of HE staining showed that all the groups with different concentrations showed positive intervention effect on psoriatic lesions,and the WGBDY high-dose group was more obvious.The expressions of IL-6,Bcl-6,ICOS and CD40L mRNA in the WGBDY low,medium and high dose groups and the western control group were significantly decreased(P<0.01).The expression levels of IL-6,Bcl-6,ICOS and CD40L protein were down-regulated in different concentration groups(P<0.01,P<0.05).Correlation analysis showed that △MPASI was negatively correlated with IL-6,Bcl-6,ICOS,CD40L mRNA and protein expression(P<0.01).Conclusion Wugong Baidu decoction may inhibit the upstream pathway of Tfh cells

关 键 词：蜈蚣败毒饮 滤泡辅助性T细胞 IL-6 BCL-6 可诱导共刺激分子 CD40L 银屑病 

分 类 号：R758.63[医药卫生—皮肤病学与性病学]