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磁性聚乳酸羟基乙酸氧化苦参碱纳米微球的制备及抗小鼠肝纤维化作用
郑智武1,陈岳祥1,陈伟忠1*,宋春燕1,钱慧1,高静2
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(1.第二军医大学长征医院消化内科,上海200003;2.第二军医大学药学院药剂学教研室,上海200433)
摘要:
目的:探讨磁性聚乳酸羟基乙酸氧化苦参碱纳米粒(M-PLGA-OM-NP)对小鼠肝纤维化的防治作用。方法:运用复乳法制备M-PLGA-OM-NP;透射电镜观察纳米粒形态。采用二甲基亚硝胺(DMN)诱导小鼠肝纤维化模型,观察M-PLGA-OM-NP干预后肝脏生化指标及病理组织改变。 结果:M-PLGA-OM-NP外观呈规则球形,平均粒径为146.5 nm,载药量为7.61%,包封率为44.8%。M-PLGA-OM-NP组(外加磁场组和非磁场组)的丙氨酸转氨酶(ALT)水平较模型组下降;光镜下肝脏的纤维化程度较模型组明显减轻,较单纯氧化苦参碱(OM)用药组也明显改善;肝星状细胞活化的标志物α-SMA的表达较模型组及单纯OM用药组明显减弱。结论:M-PLGA-OM-NP在外加磁场的作用下,可增强OM的对DMN诱导的肝纤维化的防治作用。
关键词:  肝纤维化  氧化苦参碱  聚乳酸羟基乙酸  磁性纳米粒
DOI:10.3724/SP.J.1008.2009.0500
投稿时间:2008-10-14修订日期:2009-02-24
基金项目:上海市卫生局科技发展基金(054123).
Preparation of magnetic poly D,L-lactide-co-glycolide oxymatrine nanoparticles and their preventive effect against liver fibrosis in mice
ZHENG Zhi-wu1,CHEN Yue-xiang1,CHEN Wei-zhong1*,SONG Chun-yan1,QIAN Hui1,GAO Jing2
(1.Department of Gastroenterology,Changzheng Hospital,Second Military Medical University,Shanghai 200003,China;2.Department of Pharmaceutics,School of Pharmacy,Second Military Medical University,Shanghai 200433)
Abstract:
Objective:To prepare magnetic poly D,L-lactide-co-glycolide oxymatrine nanoparticle(M-PLGA-OM-NP) and investigate its preventive effects against experimental liver fibrosis.Methods: The M-PLGA-OM-NP was prepared by multiple emulsion process and observed by transmission electron microscope(TEM).Dimethylnitrosamine (DMN)-induced liver fibrosis was established with mice.After intervention with M-PLGA-OM-NP,the expression of α-smooth muscle actin (a-SMA) in the livers of mice was detected by immunohistochemical assay and the score of liver fibrosis was determined by H-E staining and Van Gieson (VG) staining.Results: The prepared M-PLGA-OM-NP was in a regular sphere shape,with a mean diameter of 146.5 nm; the drug loading was 7.61% and the encapsulation ratio was 44.8%.The serum Alt level in the M-PLGA-OM-NP group was decreased compared with that in the model group.Light microscopy revealed that the fibrosis in the M-PLGA-OM-NP group was greatly improved compared with the model group and pure oxymatrine group.The expression of a-SMA,the marker of hepatic stellate cell activation,was obviously decreased in the M-PLGA-OM-NP group compared with that in the other groups.Conclusion: The prepared M-PLGA-OM-NP under magnetic field can reinforce the preventive effect of oxymatrine against DMN-induced experimental liver fibrosis in mice.
Key words:  liver fibrosis  oxymatrine  poly D,L-lactic-co-glycolide acid  magnetic nanoparticles