银屑Ⅰ号方对银屑病小鼠模型角质细胞增殖及外周血T淋巴细胞的干预作用  

Effects of Yinxie I Formula on keratinocyte proliferation and peripheral blood T lymphocytes in psoriatic mice model

作　　者：杭怡宁 黎锦添 查旭山[2] HANG Yi-ning;LI Jin-tian;CHA Xu-shan(First Clinical Medicine College,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

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：《中华中医药杂志》2021年第12期7333-7337,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81573980);广东省省级科技计划项目(No.2017A020215058)。

摘　　要：目的:探讨银屑Ⅰ号方对咪喹莫特(IMQ)诱导的BABL/c小鼠银屑病模型角质细胞增殖及外周血T淋巴细胞的干预作用。方法:SPF级BABL/c小鼠30只,随机分为对照组,模型组,银屑Ⅰ号方低、中、高剂量组,每组6只。除对照组外,其余各组每日于背部皮损处外涂62.5mg 5%IMQ诱导银屑病小鼠模型,银屑Ⅰ号方低、中、高剂量组小鼠于造模期间同时灌胃1.02、2.03、4.06g/mL银屑Ⅰ号方,共7d。分别评价小鼠背部皮损面积和疾病严重程度(PASI)评分、局部皮损病理变化、脾肿胀情况并采用qPCR,Western Blot及流式分析法检测皮损及外周血中维A酸受体(RAR)、维A酸X受体(RXR)表达水平及外周血T淋巴细胞分化水平。结果:与对照组比较,模型组小鼠背部皮损出现典型银屑病表现,PASI评分及脾肿胀指数显著上升(P<0.01),RAR、RXR mRNA及蛋白表达显著降低(P<0.01),CD_(3)^(+)CD_(4)^(+)、CD_(3)^(+)CD_(8)^(+)水平显著升高(P<0.01),CD_(4)^(+)/CD_(8)^(+)显著下降(P<0.01);与模型组比较,银屑Ⅰ号方各组小鼠背部皮损红斑、鳞屑相对较少、浸润程度较轻,PASI评分及脾肿胀指数随剂量增加依次减低(P<0.01),银屑Ⅰ号方高剂量组RAR、RXR mRNA及蛋白表达显著升高(P<0.05,P<0.01),CD_(3)^(+)CD_(4)^(+)、CD_(3)^(+)CD_(8)^(+)水平显著降低(P<0.01),CD_(4)^(+)/CD_(8)^(+)比值显著升高(P<0.01)。结论:银屑Ⅰ号方可有效改善银屑病小鼠病理状态及免疫失衡,其机制可能与其发挥类维A酸类药物作用调控局部皮损中RAR、RXR表达及外周血中T淋巴细胞分化水平有关,但存在剂量依赖性。Objective:To observe the effects of Yinxie I Formula(YXI F)on keratinocyte proliferation and peripheral blood T lymphocytes in imiquimod(IMQ)-induced BABL/c mice model.Methods:Thirty SPF BABL/c mice were randomly divided into control group,model group,YX I F-L group,YXI F-M group,YXI F-H group,6 mice in each group.Except for control group,other groups were applied 62.5mg 5%IMQ to the back skin lesions daily to induce psoriasis mice models.The mice in YXI F-L group,YX I F-M group,YXI F-H group were irrigated simultaneously during the modeling period together with YXI F for 7 days.The Psoriasis Area and Severity Index(PASI),spleen swelling index of mice were recorded and the pathological changes of local skin lesions were observed.RT-PCR,Western Blot and flow cytometry were used to detect mRNA,protein expression of retinoic acid receptor(RAR).Retinoic acid X receptor(RXR)and peripheral blood T lymphocyte differentiation levels.Results:On the 7th day,compared with the control group,model group showed typical psoriasis on back skin lesions,the PASI and spleen swelling index increased significantly(P<0.01),and the expressions of RAR,RXR gene and protein decreased significantly(P<0.01),the levels of CD_(3)^(+)CD_(4)^(+)and CD_(3)^(+)CD_(8)^(+) increased significantly(P<0.01),and the ratio of CD_(4)^(+)/CD_(8)^(+) decreased significantly(P<0.01).Compared with the model group,in YX I F groups,PASI and spleen swelling index were decreased(P<0.01),the expression of RAR,RXR mRNA and protein in YXI F-H group were increased(P<0.05,P<0.01),the levels of CD_(3)^(+)CD_(4)^(+) and CD_(3)^(+)CD_(8)^(+) in YXI F-H group were significantly decreased(P<0.01),the ratio of CD_(4)^(+)/CD_(8)^(+) increased(P<0.01).Conclusion:YXI F can effectively modify the pathological status and immune imbalance of psoriasis model mice.The mechanism may be related to the regulation of RAR,RXR expression level and the differentiation of T lymphocytes in peripheral blood.

关 键 词：银屑Ⅰ号方 银屑病 维A酸受体 T淋巴细胞 银屑病动物模型 

分 类 号：R285.5[医药卫生—中药学]