目的 以苦参总碱（Sophora flavescens alkaloids，SFA）为模型药物，通过制备的SFA纳米乳（SFA nanoemulsions，SFA-NEs）和SFA纳米乳凝胶（SFA nanoemulsion-based gels，SFA-NBGs）初步阐明其透皮作用机制。方法 采用扫描电子显微镜（SEM）法、HE染色法和激光扫描共聚焦显微镜（CLSM）法分别考察SFA-NEs和SFA-NBGs对小鼠皮肤角质层和皮肤超微结构的影响。结果 SEM法观察发现，正常小鼠皮肤角质层平滑光整，生理盐水处理6 h后角质层出现轻微褶皱，而经SFA-NEs和SFA-NBGs分别处理2 h和6 h后的皮肤角质层均发生不同程度的损伤；HE染色法发现，生理盐水组皮肤结构完整，SFA-NBGs组的皮肤分层结构不明显，基底层排列不清，角质层明显疏松，而SFA-NEs组皮肤分层结构紊乱，间隙增大，角质层疏松变薄；CLSM实验结果显示，对照组、SFA-NEs组和SFA-NBGs组处理后的皮肤表面的荧光较强，深处荧光较弱，且在毛囊及其附属器附近的荧光较强。结论 SFA-NEs和SFA-NBGs主要通过破坏皮肤角质层及皮肤超微结构进而透过皮肤发挥治疗作用，同时皮肤中的毛囊及其附属器对药物的透皮也发挥了一定的作用。

Objective To prepare nanoemulsions (NE) and nanoemulsion-based gels (NBGs) with Sophora flavescens alkaloids (SFA) as model drug to illuminate its mechanism of transdermal delivery basically. Methods Using scanning electron microscopy (SEM) method, HE staining method, and confocal laser scanning microscope (CLSM) method to investigate the effect of SFA-NEs and SFA-NBGs on stratum corneum (SC) and ultrastructure. Results The results of SEM showed that the SC of normal mouse was smooth and finishing. And slightly crimp the saline group after 6 h of treatment appeared, while it was damaged in varying degrees hurt after 2 h and 6 h of action by SFA-NEs and SFA-NBGs, respectively. HE staining results indicated that the skin structure of saline group was basically intact. But the hierarchy structure of SFA-NBGs group was not obvious, basal layer arranged unclearly and SC loosed apparently, as well as that the hierarchy structure of SFA-NEs group disordered, the gap increased, SC loosed and thinned. The result of confocal laser scanning microscope indicated that fluorescence in surface was stronger while weaker in depth among control group, SFA-NEs group, and SFA-NBGs group, and fluorescence in hair follicles and around its appendages was also stronger. Conclusion SFA-NEs and SFA-NBGs could permeate skin mainly through breaking SC and ultrastructure so as to perform therapeutic action. At the same time, hair follicles and its appendages play a role on drug transdermal course.

2015年公益性科研专项项目（项目编号201507002）