半乳糖化的波棱芴酮脂质体对四氯化碳致肝损伤小鼠的保护作用  

Protective effect of herpetfluorenone lactosylated liposome on acute hepatic injury induced by carbon tetrachloride in mice

作　　者：符小红 巴珂 顾健 谭睿[2] 袁志翔[3] 黄思远 

机构地区：[1]西南民族大学药学院,成都610041 [2]西南交通大学医学院,成都610081 [3]四川农业大学动物医学院药学系,成都611130

出　　处：《中药药理与临床》2017年第6期65-68,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(81573563;81274168);四川省中医药管理局科研项目(2016C062);西南民族大学研究生"创新型科研项目"(CX2016SZ033)

摘　　要：目的:以半乳糖基修饰的脂质(LAC)为肝靶向材料,制备载波棱芴酮肝靶向脂质体,考察其与波棱芴酮脂质体对CCl4致肝损伤小鼠保护作用的疗效差异。方法:采用薄膜分散法制备波棱芴酮半乳糖化脂质体、波棱芴酮脂质体,并对半乳糖化的波棱芴酮脂质体进行质量评价。体内药效实验,小鼠随机分为空白组、模型组、波棱芴酮单体组、波棱芴酮脂质体组、波棱芴酮半乳糖化脂质体组。每日给小鼠尾静脉注射生理盐水或单体、波棱芴酮脂质体、波棱芴酮半乳糖化脂质体1次,给药剂量20 mg/kg,共7天。实验末期,腹腔注射CCl_4建立小鼠急性肝损伤模型。肝脏称重,计算肝脏系数,并测定各组小鼠天门冬氨酸氨基转移酶(AST)、血清丙氨酸氨基转移酶(ALT)、肝组织匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)等指标,HE染色对肝组织进行组织病理学检查。结果:制备的波棱芴酮半乳糖化脂质体平均粒径(128.9±1.8)nm,分散系数为0.172±0.006,给药剂量为20mg/kg的体内药效结果表明,与波棱芴酮脂质体组相比,半乳糖化的波棱芴酮脂质体组显著降低CCl_4致急性肝损伤模型小鼠肝脏系数和血清ALT、AST水平,肝组织病理形态损伤减轻,肝脏SOD和GSH-Px活性升高,减少肝组织匀浆中MDA的含量。结论:经半乳糖基修饰的脂质体能够提高药物在肝脏的聚集,增强CCl_4致化学性肝损伤小鼠的保护作用。Objective： To use galactosyl-modified lipid（ LAC） as the liver targeting material to prepare the herpetfluorenone liver targeting liposome,and investigate differences in efficacy that protective effects of herpetfluorenone lactosylated liposome and herpetfluorenone liposome on liver injury induced by CCl_4 in mice. Methods： The herpetfluorenone lactosylated liposome and herpetfluorenone liposome were prepared by film dispersion method,the quality of herpetfluorenone lactosylated liposome was evaluated. In vivo pharmacodynamics experiment,mice were randomly divided into the control group,the model group,herpetfluorenone monomer group,herpetfluorenone liposome group,herpetfluorenone galactosylated liposome group. Mice were injected with saline or monomer,herpetfluorenone liposome and herpetfluorenone galactosylated liposome 1 time daily at a dose of 20 mg/kg for 7 days. At the end of the experiment,the model of acute liver injury was established by intraperitoneal injection of CCl_4. Liver coefficients were calculated after livers were weighed,activities of alanine aminotransferase（ ALT）and aspartate aminotransferase（ AST） in serum were detected in all groups; Contents of malonaldehyde（ MDA） in hepatic homogenate were determined and activities of superoxyde dismutase（ SOD） and glutathionperoxidase（ GSH-Px） in hepatic homogenate were analyzed. In addition,pathological changes of liver tissues were also observed. Results： The average particle size of herpetfluorenone galactosylated liposome was（ 128. 9 ± 1. 8） nm,and the dispersion coefficient was 0. 172 ± 0. 006. The efficacy results which the dose was 20 mg/kg in vivo showed that,herpetfluorenone galactosylated liposome significantly reduced liver indexes and levels of serum ALT and AST in mice with acute liver injury induced by CCl4,the pathologic morphology of liver tissue was lightly damaged,while activities of SOD and GSH-Px were increased,contents of MDA were obviously decreased,compared with the herpetfluorenone liposome gr

关 键 词：波棱芴酮 肝靶向 脂质体 急性肝损伤 

分 类 号：R285.5[医药卫生—中药学]