目的 比较穴位与非穴位皮肤的电阻、角质层厚度、生物化学组成，并研究白芥子涂方经穴位和非穴位给药芥子碱的渗透特性，探讨皮肤生物物理学性质对芥子碱经皮给药的影响，为白芥子涂方临床穴位贴敷预防和治疗哮喘提供实验支持。方法 以自制装置测定穴位与非穴位皮肤电阻；皮肤组织切片经HE染色后，在光学显微镜下测量皮肤和角质层厚度；以激光显微拉曼光谱法比较皮肤的生物化学组成；以芥子碱为评价指标，采用HPLC法定量，用Franz扩散池法研究白芥子涂方离体经穴位和非穴位皮肤的渗透特性；在体渗透实验采用胶带粘贴法剥离角质层，比较穴位与非穴位皮肤各层中药物的分布。结果 穴位皮肤电阻在给药前后各时间点均显著低于非穴位皮肤（P＜0.05）；穴位皮肤角质层厚度显著低于非穴位（P＜0.05）；激光显微拉曼光谱显示穴位与非穴位皮肤的生物化学组成基本一致。给药24 h后，离体实验中芥子碱经穴位皮肤的单位面积累积透过量是经非穴位皮肤的6.8倍（P＜0.05）；穴位皮肤稳态透皮速率是非穴位的6.1倍；离体透皮实验和在体渗透实验中，24 h皮肤中药物滞留量均为穴位＞非穴位（P＜0.05），各时间点角质层中药物滞留量均为穴位＞非穴位（P＜0.05）。结论 芥子碱经穴位皮肤的透过量和皮肤滞留量均显著高于经非穴位皮肤。穴位皮肤的低电阻、角质层薄有利于药物的经皮吸收和贮存，验证了涂方临床使用以穴位经皮给药的科学性。

Objective To compare the electric resistance, stratum corneum thickness, and biochemical composition in acupoint and non-acupoint skin, and the osmotic properties of sinapine by acupoint and non-acupoint administration with Baijiezi Tufang (Baijiezi liniment prescription), to investigate the effect of dermal biophysical characteristics on cutaneous administration of sinapine, and to provide the experimental support of acupoint transdermal of Baijiezi Tufang for the treatment of asthma. Methods Skin electrical resistance was measured with a specially designed meter, the thickness of stratum corneum was detected through microscope after the skin slice was stained by HE, and the skin biochemistry ingredients were compared by laser Raman spectroscopy. The permeability through acupoint and non-acupoint skin was examined with the modified Franz diffusion cell in vitro and tape-stripping in vivo, using sinapine as index. The content of sinapine was determined by HPLC. In in vivo permeability experiment, the stratum corneum was isolated and the distribution of drugs in various layers of acupoint and non-acupoint was compared. Results The dermal resistance in acupoint was lower than that in non-acupoint (P < 0.05) and the stratum corneum of acupoint was thinner than that of non-acupoint (P < 0.05). However, the biochemistry ingredients of them were almost the same. The 24 h cumulative amount through the acupoint skin was about 6.8 times as that through the non-acupoint skin, and the steady-state flux of sinapine across acupoint skin was 6.1 times as that across in non-acupoint skin. Sinapine retention in acupoint skin was significantly higher than that in non-acupoint skin (P < 0.05) both in vitro and in vivo after 24 h of administration, and the retention in stratum corenum of acupoint was also higher than that in stratum corneum of non-acupoint at different time points within 24 h. Conclusion The permeation and retention of sinapine in Baijiezi Tufang through acupoint skin are higher than those through non-acupoint skin, which relates to the lower electrical resistance and thinner stratum corenum of acupoint skin. It suggests the rationale evidence for acupoint administration in clinic application of Baijiezi Tufang.

国家自然科学基金资助项目（81073066）