苦参碱微乳经皮给药在小鼠体内分布及对兔耳增生性瘢痕预防作用的研究  

Distribution of Matrine Loaded Microemulsion and its Precentive Effect on Hyperplastic Scar of Rabbit Ears

作　　者：吕建华 魏红 张振[2] 郭瑞臣[2] 

机构地区：[1]山东医学高等专科学校,山东济南250002 [2]山东大学齐鲁医院临床药理研究所,山东济南250012

出　　处：《时珍国医国药》2011年第3期572-575,共4页Lishizhen Medicine and Materia Medica Research

基　　金：山东省自然科学基金(No.Y2007C078)

摘　　要：目的建立血浆苦参碱的GC-MS联用分析法,测定经皮给药后苦参碱在小鼠肺、肾、皮、脾、肝和心组织中的含量;观察苦参碱微乳对兔耳增生性瘢痕的预防作用。方法将苦参碱微乳经小鼠背部皮肤给药,用GC-MS分析法测定苦参碱在小鼠各组织中浓度分布;15只家兔随机分为1组、2组和模型对照组,各组麻醉后,兔耳全皮层至软骨膜损伤造瘢痕模型。1组和2组分别预防性给苦参碱微乳,模型对照组给空白微乳;生物光学显微镜下观察3组兔耳增生性瘢痕病理改变情况。结果苦参碱在32～800 ng.ml-1范围内线性关系良好(r=0.993 5),最低检出限量1 ng.ml-1,日间和日内RSD均小于2.9%,绝对回收率为70.0%～78.6%。苦参碱微乳经皮给药后,苦参碱在小鼠组织中的分布由高到低依次是肺、肾、皮、脾、肝和心,肺中的苦参碱含量明显高于其他组织(P=0.01);与模型对照组相比,苦参碱微乳对1、2组家兔耳部创伤有明显的预防增生性瘢痕的作用。结论 GC-MS方法专属、准确、灵敏,可用以测定组织中苦参碱的含量。苦参碱微乳对家兔耳部创伤有明显的预防增生性瘢痕的作用;由于苦参碱在小鼠肺中含量高,可以推测苦参碱微乳,不仅可以预防创伤性瘢痕增生,而且还可以作为临床预防肺纤维化用药,具有良好的开发应用前景。Objective To develop a highly sensitive,simple and selective gas-chromatography mass spectrometry（GC/MS） method for the determination of matrine after percutaneous administration of matrine-loaded microemulsion and to investigate the preventive effect of matrine-loaded microemulsion hyperplastic scar of rabbit ears. Methods The content of matrine in mice was determined by GC/MS after administration of matrine-loaded microemulsion.Animal model with hyperplastic scar in rabbit ears was established and 15 rabbits were divided in NO.1 group,NO.2 group and NO.3 model control group.After individual prophylactic percutaneous administration of matrine-loaded microemulsion in NO.1 group,NO.2 group and the percutaneous administration of non-matrine-loaded microemulsion to NO.3 model control group,the pathological changes of hyperplastic scar in the three groups were observed. Results The linearity was ranged from 32 to 800 ng/ml.The RSD（%） of within-day and between-day were all less than 2.9%.The absolute recovery was 70.0%～78.6%.After percutaneous administration of matrine-loaded microemulsion,the order of matrine content in mice was： lungkidneyskinspleenliverheart.The content of matrine in lung was significantly higher than that of other tissues（P=0.01）.Compared with the NO.3 model control group,the NO.1 and NO.2 groups had significant effect on the hyperplastic scar of rabbit ears. Conclusion The GC/MS method was successfully applied to quantify the low matrine concentration in samples.Microemulsion has effective impact on hyperplastic scar on rabbit ears.

关 键 词：苦参碱 经皮吸收制剂 组织分布 增生性瘢痕 

分 类 号：R285.5[医药卫生—中药学]