壳聚糖降解衍生物的抗氧化活性及对药物性肝损伤纤维化的预防作用  

Antioxidant Activity and Preventive Effects of Chitosan Degradation Derivatives on Drug-induced Liver Injury Fibosis

作　　者：张迪[1] 邢宇[1] 王杨[1] 孔敏[1] 李新莉[1] 

机构地区：[1]大连医科大学生物技术系,辽宁大连116044

出　　处：《中国药房》2017年第25期3498-3501,共4页China Pharmacy

基　　金：辽宁省教育厅科学研究一般项目(No.L2016004)

摘　　要：目的:研究壳聚糖(CTS)降解衍生物的体外抗氧化活性及对药物性肝损伤纤维化的预防作用。方法:采用酸水解法制备不同水解时间(3、6、8、10 h)的CTS降解衍生物CTS-3、CTS-6、CTS-8、CTS-10,测定CTS及其降解衍生物的黏均分子量和脱乙酰度,通过检测其对1,1-二苯基-2-三硝基苯肼(DPPH)和超氧负离子(O_2^-)自由基的体外清除能力评价其抗氧化活性。以CTS-10进行体内肝损伤纤维化的预防实验,将小鼠随机分为正常对照组(水)、模型组(水)和CTS-10高、中、低剂量组(100、50、25 mg/m L),每组8只,每天ig给药0.2 m L,连续24 d后停药;继而连续ig盐酸左氧氟沙星7d建立药物性肝损伤模型(正常对照组除外)。采用Western blot法检测小鼠肝组织中肿瘤坏死因子α(TNF-α)、转化生长因子β1(TGF-β_1)和饰胶蛋白聚糖(Decorin)蛋白的表达。结果:CTS、CTS-3、CTS-6、CTS-8、CTS-10的黏均分子量分别为21.70×10~4、6.70×10~4、6.30×10~4、5.01×10~4、4.87×10~4,脱乙酰度分别为83.44%、74.62%、67.28%、64.83%、54.23%;对DPPH和O_2^-自由基均有一定的清除能力,其中CTS-10清除能力最强,分别为25.47%和56.31%。与正常对照组比较,模型组小鼠肝组织中TNF-α、TGF-β_1和Decorin蛋白表达均增强(P<0.05);与模型组比较,CTS-10中、高剂量组小鼠肝组织中TNF-α、TGF-β_1和Decorin蛋白表达均减弱(P<0.01)。结论:CTS降解衍生物中CST-10的黏均分子量和脱乙酰度较低,具有较强的体外抗氧化活性,对小鼠药物性肝损伤纤维化有一定的预防作用。OBJECTIVE： To study the in vitro antioxidant activity of chitosan （CTS） degradation derivatives and its preventive effects on drug-induced liver injury fibosis. METHODS： Acid hydrolysis method was used to prepare the CTS degradation deriva- tives CTS-3, CTS-6, CTS-8, CTS-10 for different hydrolysis time （3, 6, 8, 10 h）. The viscosity-average relative molecular mass and deacetylation degree of CTS and its degradation derivatives were determined, and its antioxidant activity was evaluated by de- tecting its in vitro scavenging ability on 1,1-diphenyl-2-trinitrophenylhydrazine （DPPH） and superoxide anion （02-） radicals. Us- ing CTS-10 for in vivo liver injury fibosis prevention test, mice were randomly divided into normal control group （water）, model group （water）, CTS-10 high-dose, medium-dose, low-dose groups （100, 50, 25 mg/mL）, 8 in each group. Mice were intragastri- cally administrated 0.2 mL, then withdrawal after continuous 24 d. Then levofloxacin hydrochloride was intragastrically given for 7 d to establish drug-induced liver injury model （except for normal control group）. Western blot method was used to detect the expres- sions of tumor necrosis factor α （TNF-α）, transforming growth factor β1 （TGF-β1） and Decorin protein in liver tissue of mice. RE- SULTS： The viscosity-average relative molecular mass of CTS, CTS-3, CTS-6, CTS-8, CTS-10 were 21.70×10^4, 6.70×10^4, 6.30×10^4, 5.01×10^4, 4.87×10^4; and deacetylation degree were 83.44%, 74.62%, 67.28%, 64.83%, 54.23%, respectively. All of them had certain scavenging ability on DPPH and O2-, in which, CTS-10 was the strongest （25.47% and 56.31% ）. Compared with nor- mal control group, expressions of TNF-α, TGF-β1 and Decorin protein in liver tissue in model group were enhanced （P-〈0.05）. Compared with model group, expressions of TNF-α, TGF-β1 and Decorin protein in liver tissue in CTS-10 medium-dose and high-dose groups were weakened （P〈0.01）. CONCLUSIONS： The viscosity-average relativ

关 键 词：壳聚糖 降解衍生物 抗氧化活性 药物性肝损伤 肝纤维化 小鼠 

分 类 号：R285.5[医药卫生—中药学]