秦艽鳖甲散调控Toll样受体4信号通路改善银屑病小鼠皮损作用机制研究  

Mechanism of Qinjiao Biejia Powder in Improving Psoriasis Skin Lesions in Mice by Regulating the Toll-like Receptor 4 Signaling Pathway

作　　者：胡幸 赵颖[2] 李领娥 胡素叶 HU Xing;ZHAO Ying;LI Ling′e;HU Suye(Department of Dermatology,Guang′anmen Hospital,Ji′nan Hospital/Ji′nan Municipal Hospital of Traditional Chinese Medicine,Ji′nan 250012,China;Department of Dermatology,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Ji′nan 250011,China;Department of Dermatology,Shijiazhuang Hospital of Traditional Chinese Medicine,Shijiazhuang 050051,China)

机构地区：[1]广安门医院济南医院/济南市中医医院皮肤科,济南250012 [2]山东中医药大学附属医院皮肤科,济南250011 [3]石家庄市中医院皮肤科,石家庄050051

出　　处：《世界中医药》2024年第17期2590-2595,共6页World Chinese Medicine

基　　金：国家重点研发计划“中医药现代化研究”重点专项(2018YFC1705300)——银屑病“新血证论”理论体系构建与实践;山东省自然科学基金项目(ZR2015HL121);2022年济南市卫生健康委员会中医药科技计划专项(2022-中-21项)。

摘　　要：目的:研究秦艽鳖甲散改善银屑病小鼠皮肤损伤和炎症反应的分子机制。方法:将60只小鼠按照随机数字表法随机分为对照组、模型组、甲氨蝶呤组(1 mg/kg)及低剂量、中剂量、高剂量秦艽鳖甲散组(0.98、1.95、3.90 g/kg)。除对照组仅剔除毛发,其余各组均使用咪喹莫特构建银屑病小鼠模型。苏木精-伊红(HE)染色检测皮损组织病理变化;银屑病面积与严重性指数评分(PASI)评估皮损程度;酶联免疫吸附试验法(ELISA)检测血清炎症介质水平;实时萤光定量PCR(qRT-qPCR)检测白细胞介素-17(IL-17)、白细胞介素-23(IL-23)、白细胞介素-22(IL-22)、白细胞介素-6(IL-6)、Toll样受体4(TLR4)mRNA表达水平;免疫组织化学检测NOD样受体热蛋白结构域相关蛋白3(NLRP3)表达水平;蛋白免疫印迹检测NLRP3、TLR4/NF-κB通路相关蛋白表达水平。结果:与模型组比较,甲氨蝶呤组及低剂量、中剂量、高剂量秦艽鳖甲散组小鼠皮损状态明显改善;PASI评分明显降低;血清炎症介质水平、NLRP3及TLR4/NF-κB通路相关蛋白水平明显降低(均P<0.05)。结论:秦艽鳖甲散能够改善银屑病小鼠皮肤损伤和炎症反应,可能与抑制TLR4/NF-κB通路,下调NLRP3表达有关。Objective:To investigate the molecular mechanisms of Qinjiao Biejia Powder in improving skin lesions and inflammatory response in mice with psoriasis.Methods:Sixty mice were randomly divided into a control group,a model group,a methotrexate group(1 mg/kg),and low-dose,medium-dose,and high-dose Qinjiao Biejia Powder groups(0.98,1.95,and 3.90 g/kg,respectively)follow the random number table method.The control group only received hair removal,and the psoriasis mouse model was established using imiquimod in other groups.Hematoxylin-eosin(HE)staining was used to observe histopathological changes in the skin lesions.The psoriasis area and severity index(PASI)was used to assess the degree of skin lesions.Enzyme-linked immunosorbent assay(ELISA)measured serum levels of inflammatory mediators.Quantitative real-time PCR(qRT-PCR)detected mRNA expression levels of interleukin-17(IL-17),interleukin-23(IL-23),interleukin-22(IL-22),interleukin-6(IL-6),and Toll-like receptor 4(TLR4).Immunohistochemistry assessed the expression of NOD-like receptor protein 3(NLRP3),and Western blot analyzed the expression levels of NLRP3 and proteins related to the TLR4/NF-κB pathway.Results:Compared with the model group,the methotrexate group and the low-dose,medium-dose,and high-dose Qinjiao Biejia Powder groups showed significant improvement in skin lesions,notably reduced PASI scores,and significantly decreased serum levels of inflammatory mediators,as well as the expression of NLRP3 and TLR4/NF-κB pathway-related proteins(all P<0.05).Conclusion:Qinjiao Biejia Powder can ameliorate skin lesions and inflammatory responses in mice with psoriasis,likely through the inhibition of the TLR4/NF-κB pathway and downregulation of NLRP3 expression.

关 键 词：银屑病 秦艽鳖甲散 TOLL样受体4 核因子ΚB NOD样受体热蛋白结构域相关蛋白3 皮肤损伤 炎症反应 银屑病面积与严重性指数评分 

分 类 号：R289.5[医药卫生—方剂学] R275[医药卫生—中药学]