苦参和土茯苓联用改善小鼠银屑病样皮损的作用机制  

Investigating the effect and mechanism of Sophorae Flavescentis Radix andRhizoma Smilacis Glabrae combination in ameliorating psoriatic lesions

作　　者：武兴康 王鹭 李洋[1,2] 马瑜爽 秦雪梅 WU Xing-kang;WANG Lu;LI Yang;MA Yu-shuang;QIN Xue-mei(Modern Research Center for Traditional Chinese Medicine,the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,Shanxi University,Taiyuan 030006,China;Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province,Taiyuan 030006,China;Shanxi Key Laboratory of Redevelopment of Famous Local Traditional Chinese Medicines,Taiyuan 030006,China)

机构地区：[1]山西大学化学生物学与分子工程教育部重点实验室,中医药现代研究中心,山西太原030006 [2]地产中药功效物质研究与利用山西省重点实验室,山西太原030006 [3]名优晋药再开发山西省重点实验室,山西太原030006

出　　处：《中国药理学通报》2024年第1期171-180,共10页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金(No 82304319);山西省应用基础研究计划项目(No 202203021221010);名优晋药再开发山西省重点实验室(No 202104010910001)。

摘　　要：目的采用62.5 mg咪喹莫特乳膏诱导的小鼠银屑病样皮损模型,探索苦参和土茯苓联用外治银屑病的作用及其机制。方法首先通过银屑病进行期和复发期的小鼠模型,结合HE染色,评价其外治银屑病的作用;其次采用免疫组化研究苦参和土茯苓联用对银屑病的核心病理机制——角质形成细胞异常增殖与皮肤免疫微环境正反馈环路的干预作用;最后利用代谢组学探索苦参和土茯苓联合外用是否通过调节银屑病中炎症、脂质相关代谢通路等治疗银屑病。结果苦参和土茯苓联用改善小鼠银屑病样皮损;有效减弱小鼠银屑病痊愈后复发,药效与本维莫德相当,并且抑制小鼠表皮角质形成细胞的增殖和减少皮肤中T细胞的数量,调节花生四烯酸、鞘脂、色氨酸、苯丙氨酸等代谢通路。结论苦参和土茯苓联合外用通过抑制表皮角质形成细胞的增殖和减少皮肤中T细胞的数量改善小鼠银屑病样皮损及调节代谢干预其复发,本研究提供了一种减缓银屑病复发的潜在外用治疗药物。Aim In this study,a mouse model of psoriasis-like lesions induced by 62.5 mg imiquimod was used to explore the effect and mechanism of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination for the topical treatment of psoriasis.Methods Firstly,the topical administration of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination for treating psoriasis in progressive and recurrent stages was evaluated by psoriatic mouse model and HE staining.Secondly,immunohistochemistry was used to study the regulatory effects of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination on the pivotal pathological mechanism of psoriasis-the positive feedback loop between the abnormal proliferation of keratinocytes and skin immune microenvironment.Finally,metabolomics technology was used to explore whether Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination topically treat psoriasis by regulating inflammation-related metabolism and lipid metabolism pathways.Results The combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae alleviated psoriasis-like lesions in mice.It effectively relieved the recurrence after the cure of psoriatic lesions in mice,and the efficacy is comparable to that of benweimod.The combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae inhibited the proliferation of mouse epidermal keratinocytes and reduced the number of T cells in the skin.The potential molecular mechanism was that the combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae regulated arachidonic acid metabolism,sphingolipid metabolism,tryptophan metabolism and phenylalanine metabolism.Conclusions The combination of Sophora Flavescens Radix and Rhizoma Smilacis Glabrae can relieve psoriasis-like lesions in mice by inhibiting the proliferation of epidermal keratinocytes and reducing the number of T cells in the skin and regulating metabolism to intervene psoriasis recurrence.This study provides a potential topical drug of psoriasis for relievi

关 键 词：银屑病 苦参 土茯苓 机制 角质形成细胞 免疫微环境 代谢组学 

分 类 号：R-332[医药卫生] R282.71R641R758.63