三伏贴穴位给药防治哮喘具有广泛临床实践基础和确切疗效，但其经皮给药作用机理尚不明确，限制了该特色疗法的发展。我们前期证实穴位对三伏贴经皮给药具有促渗和免疫增效作用，但其促渗和增效的客观物质基础有待探明。我们利用脂质/蛋白组学技术比较穴位与非穴位角质层差异性，并利用免疫荧光-CLSM等比较两者活性表皮层的TJs，验证假设之一：穴位皮肤渗透屏障具有促渗的微观物质基础。利用CLSM和流式细胞术结合ELISA测定相关细胞因子等研究三伏贴作用前后皮肤免疫屏障和肺组织的分子事件，验证假设之二：三伏贴以DCs为靶细胞启动皮肤免疫，并通过改变表皮LCs-真皮DCs-肺DCs的分布、表型和功能等级联调控肺免疫稳态。研究结果以现代免疫学、皮肤生理学和经皮给药制剂理论相结合阐明三伏贴防治哮喘的穴位效应物质基础，启发和推动穴位经皮给药机理探讨，为中医内病外治提供研究思路，并为利用现代技术研究传统中医理论提供范例。

As radical cure for asthma does not yet exist, topical application of Sanfu patch is widely used and has significant therapeutic effect in the clinical treatment of asthma, but its mechanism for percutaneous delivery is not fully understood. Our previous studies demonstrated that topical application of Sanfu patch in acupoints could enable the targeting distribution of drug within the lung, resulting in improved efficacy, which was related to its pharmacokinetics. Sanfu patch could also enhance drug permeation and immunopotentiation. However, the fundamental molecular mechanism remains unclear. This study aims to illustrate the mechanism. Based on permeation and immune barriers of skin, we hypothesize the following: 1. Acupoints can enhance drug permeation and reserve a drug depot in the skin, which is related to the microcosmic substance-elements of epidermis; 2. Dendritic cells (DCs) act as the immune target of acupoint application and cause the activation of skin immune response, the changes of tissue distribution, cell phenotype, and functions of epidermal LCs, dermal DCs, and lung DCs lead to the cascade regulation of acupoint application of Sanfu patch for maintaining the immune homeostasis of lung. In this project, we use the following studies to verify our hypothesis: Firstly, proteomics and lipidomics will be performed to evaluate the protein and lipid differences between acupoint and non-acupoint stratum corneum. Secondly, immunohistochemical combined with confocal laser scanning microscope (CLSM) and RT-qPCR will be used to study the expression of tight junctions of viable epidermis. The lower content of some proteins, lipids, and tight junctions under acupoint epidermis contribute to the permeation enhancing effects. Then, we compared the differences of Langerhans cells (LCs), dermal DCs, and lung DCs based on their distribution, phenotype, and function prior to and after Sanfu patch treated. The skin immune response will be evaluated based on the changes of LCs, DCs, and cytokines. At the same time, the changes of DCs and cytokines in the lung will be compared too, and the asthma in the lung will be evaluated. Multiple studies combined with modern immunology, skin physiology, and percutaneous delivery system can explain the acupoint mechanism of Sanfu patch for the prevention and treatment of asthma and inspire further studies of the mechanism of acupoint application. Moreover, these studies can motivate new research ideas for external treatment of Chinese medicine and set an example for traditional Chinese medicine theory by using modern technology.