[关键词]
[摘要]
目的 考察顽癣敌软膏 (WXD) 对银屑病的作用及机制。方法 采用小鼠背部皮肤连续涂抹 7 d 咪喹莫特建立银屑病模型。时-效关系研究,设正常对照组,模型对照组,WXD 第 1、2、3、4 天给药组及糠酸莫米松组,每日涂抹药物一次。量-效关系研究,设正常对照组,模型对照组,WXD 1、2、3 次组及糠酸莫米松组,从造模第 4 天开始给药。通过银屑病皮损面积和严重程度指数(PASI)和病理观察进行药效评价;采用qRT-PCR 法检测皮肤 TNF-α 和 IL-1β mRNA 的表达;ELISA 法检测 IL-23、IL-17A、5-HT、组胺含量;免疫组织化学法检测皮肤髓过氧化物酶(MPO)水平和 p-JAK2 表达;Western Blot 法检测 p-STAT3 蛋白表达。结果 时-效关系研究结果显示,WXD 第 1、2、3、4 天给药组的 PASI、棘层厚度、棘层杵状突起长度、棘层杵状突起面积/棘层面积均较模型组明显降低(P<0.05,P<0.01)。量-效关系研究结果显示,WXD 1 次组效果更佳(P<0.05,P<0.01)。WXD 可明显降低银屑病小鼠皮肤组织 MPO、p-JAK2、p-STAT3 蛋白表达及IL-23、IL-17A 水平,降低皮肤 TNF-α 及 IL-1β mRNA 表达,降低血清 5-HT 和组胺水平(P<0.05,P<0.01)。结论 顽癣敌软膏在造模同时进行预防给药和在银屑病症状明显时进行治疗给药的两种给药方式均有效,以每日给药1次治疗银屑病效果最佳,其机制与下调 JAK2/STAT3 信号通路抑制炎症反应有关。
[Key word]
[Abstract]
Objective To investigate the effect and mechanism of Wanxuandi Ointment (WXD) on imiquimod-induced psoriasis in mice. Methods A psoriasis mice model was established by applying imiquimod to the hairless area on the back of the mice for 7 consecutive days. In the study of the time-effect relationship,mice were randomly separated into normal group,model group,groups of 1st,2nd,3rd,4th day of WXD-medication,and mometasone furoate (MF) group. The corresponding ointment was rubbed into the skin once daily. In the study of dose-effect relationship,mice were randomly separated into normal group,model group,groups of 1,2,3 time of WXD-medication,and MF group. These drugs were rubbed into the skin at the 4th day of modeling. The psoriasis area and severity index (PASI) and pathological observation were used to evaluate the effect of WXD on psoriasis. The mRNA expressions of TNF-α and IL-1β in the skin were detected by qRT-PCR. The content of IL-23,IL-17A,5-HT and histamine were detected by ELISA. The protein expressions of myeloperoxidase (MPO) and p-JAK2 in the skin were detected by immunohistochemistry. The protein expression of p-STAT3 was detected by Western Blot. Results The results of time-effect relationship showed that PASI,thickness of stratum spinosum,length of drumstick-shaped protrusion of stratum spinosum,area of drumstick-shaped protrusion of stratum spinosum /stratum spinosum area were obviously reduced in groups of 1st,2nd,3rd,4th day of WXD-medication (P<0.05,P<0.01). The results of dose-effect relationship suggested that all above mentioned indexes in group of 1 time of WXD-medication were also significantly decreased (P<0.05,P<0.01). Additionally,WXD significantly reduced the protein expression of MPO,p-JAK2,p-STAT3,IL-23 and IL-17A,and the mRNA expressions of TNF-α and IL-1β in skin tissues of psoriasis mice, as well as the serum levels of 5-HT and histamine (P<0.05, P<0.01). Conclusion WXD administration for prevention during the model establishment and therapeutic treatment of WXD in the stage of obvious psoriasis symptoms are effective,once-daily administration of WXD is considered be the best treatment for psoriasis.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金青年项目(82104504);广州市科技计划项目 (202102021263);广东省教育厅生物医药与健康重点领域专项(2021ZDZX2026);广州市科技局基础与应用基础项目之广州市重点实验室建设项目 (2024A03J0360);国家中医药传承创新中心科研专项(2023ZD01)