基于TRPV1通道探讨白芥子涂方穴位经皮给药促透和免疫增效的机制

哮喘尚无有效的根治方法和药物，西医糖皮质激素及支气管扩张药对症治疗具有严重副作用，而中医白芥子凃方穴位经皮给药防治哮喘具有广泛临床实践基础及确切的疗效，但目前其经皮给药的作用机理尚未明确，限制了该特色疗法的发展。我们推测其作用机理之一可能是通过激活皮肤TRPV1通道而促进药物渗透，同时发挥免疫增效作用。本项目在前期证实穴位对白芥子凃方经皮给药具有促渗和免疫增效作用的基础上，利用免疫组化、激光共聚焦，结合RT-PCR，对穴位与非穴位的TRPV1表达进行比较，并研究该通道激活后皮肤屏障功能及渗透特性，同时比较皮肤免疫启动和机体免疫应答，验证TRPV1激活可促进白芥子凃方经穴渗透且发挥免疫增效作用的假设。研究结果以神经生物学、免疫学和经皮给药制剂理论相结合阐明白芥子凃方给药防治哮喘的作用机理，启发和推动穴位经皮给药的机理探讨，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。

Asthma is presently incurable, and there are severe side effects when glucocorticoids or broncholilator agents are administered for controlling the symptoms with the disease in western medicine. Baijiezi Tufang, a traditional Chinese medicine, is widely and effectly used for clinical prevention and treatment of the common winter diseases of asthma and bronchitis by acupuncture point percutaneous administration in the summer. However, the exact mechanism of action of the medication remains unclear, which limits its development in clinical application. In the present study, one of the action mechanisms of the medication was supposed to enhance the permeation of drugs and improve the immunity function through activation of TRPV1 channel in the acupuncture point skin. The enhancement of permeation and improvement of immunity function were confirmed in our previous study. In this project, comparation of TRPV1 expression between acupoint and non-acupoint was carried out with immunohistochemical methods combining with CLSM and RT-PCR. After the activation of TRPV1,skin barrier was researched by measuring the value of TWEL, the permeability of drugs was comparatively evaluated with TRPV1+/+ and TRPV1-/- C57BL/6 mice,and both of the skin and body immunity function were evaluated from organ, cell, and cytokine. The above hypothesis of permeation enhancement and immunity function improvement through the activation of TRPV1 channel will be confirmed. The results will elucidate the possible mechanism underlying the medication from neurobiology, immunology, and percutaneous delivery, which will promote the elucidation of acupuncture percutaneous delivery, benefit the new research approach to external treatment for internal diseases, and set an example for how to use modern molecular biology technology to study the Traditional Chinese Medicine.