骨痛灵酊短时给药的透皮特性和抗炎效果研究

Transdermal characteristics and anti-inflammatory effects of Gutongling tincture after short-term administration

目的研究骨痛灵酊的经皮渗透特性与抗炎药效,评估其短时给药的有效性。方法分析骨痛灵酊的主要活性成分,选择其中3种作为透皮实验检测指标,并建立LC-MS/MS法测定其含量;检测3种成分的累积渗透量和皮层滞留量。造角叉菜胶大鼠足肿胀模型,测量造模给药前后大鼠的体重和足趾容积变化;用ELISA检测组织中的白细胞介素(IL)-1β、肿瘤坏死因子α(TNF-α)、IL-10的含量,用qPCR检测组织中5-羟色胺(5-HT)、一氧化碳合成酶(iNOS)、IL-6的mRNA水平。结果与给药24 h组比较,体外给药1 h组3种成分的累积渗透量相当;3种成分在角质层的滞留量在给药1 h后基本达到饱和,在表皮真皮层的滞留量随给药时间延长而逐步升高。骨痛灵酊可快速减轻大鼠足趾肿胀程度和炎症;其消肿抗炎机制可能与下调IL-1β、5-HT、iNOS、IL-6的水平有关。结论骨痛灵酊短时给药可达到很好的透皮吸收和消肿抗炎效果,且安全性良好。

OBJECTIVE To study the percutaneous permeability characteristics and the anti-inflammatory effects of Gutongling tincture(GT),and to evaluate the feasibility of short-term administration of GT.METHODS The main chemical components of GT were analyzed,and three components were selected as the target for transdermal assay.LC-MS/MS methods was established,and the cumulative penetration amount and cortex retention amount of the three components were analyzed.The foot edema model in rats was established by injecting carrageenan,and the body weight and toe volume of the rats were measured before and after drug administration.The protein level of IL-1β,TNF-α,IL-10 in tissues were detected by ELISA,and the mRNA levels of 5-HT,iNOS,and IL-6 in tissues were detected by qPCR.RESULTS The cumulative penetration amount of the three components between the 1 h group and the 24 h group were similar.The retention amount of the three components in stratum corneum reached saturation after 1 h of administration,but the retention amount of the three in epidermis and dermis gradually increased with the prolongation of administration time.GT could significantly reduce the degree of foot edema and inflammation in rats in a short time.Its anti-edema and anti-inflammation mechanism might be related to down-regulation of IL-1β,5-HT,iNOS and IL-6.CONCLUSION Short-term administration of GT achieves good transdermal absorption and anti-inflammation effects with a favorable safety profile.