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

发布时间：2018-03-10 01:01

本文选题：壳聚糖　切入点：降解衍生物　出处：《中国药房》2017年25期 　论文类型：期刊论文

【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(P0.05);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(P0.01)。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。
[Abstract]:Objective: To study the effect of chitosan (CTS) antioxidant activity in vitro degradation of derivatives and the preventive effect of drug-induced liver injury and fibrosis. Methods: to prepare different hydrolysis time by acid hydrolysis method (3,6,8,10 h) CTS CTS-6, CTS-8 degradation derivatives CTS-3, CTS-10, CTS, and the degradation of derivatives determination of viscosity average molecular weight and removal acetylation degree, by detecting the 1,1- of two phenyl -2- three 4-dinitrophenylhydrazine (DPPH) and superoxide anion (O_2~-) scavenging free radicals in vitro evaluation of its antioxidant activity. Prevention of experimental fibrosis liver injury in vivo by CTS-10, the mice were randomly divided into normal control group (water), model group (water) and CTS-10 high, low dose group (100,50,25 mg/m L), 8 rats in each group, Ig daily administration of 0.2 m L for 24 d after discontinuation of levofloxacin hydrochloride; then continuous Ig 7d to establish the model of drug-induced liver injury (except the normal control group) by Western blot assay. Tumor necrosis factor alpha in liver tissue of mice (TNF- alpha), transforming growth factor beta 1 (TGF- ~ _1) and decorin (Decorin) protein expression. Results: CTS, CTS-3, CTS-6, CTS-8, CTS-10 molecular weight 21.70 * 10~4,6.70 * 10~4,6.30 * 10~4,5.01 * ~4,4.87 * 10 10~4 respectively, the degree of deacetylation was 83.44%, respectively, 74.62%, 67.28%, 64.83%, 54.23%; DPPH and O_2~- radicals have certain antioxidant ability, which CTS-10 had the strongest ability in clearing up, respectively, compared with the normal control group and 25.47% 56.31%., TNF- alpha in the livers of model mice, enhanced expression of TGF- beta _1 and Decorin protein (P0.05); compared with the model group, CTS-10, TNF- alpha liver in high dose group, the expression of TGF- beta _1 and Decorin proteins were significantly decreased (P0.01). Conclusion: CST-10 degradation of CTS derivatives in molecular weight and a low degree of deacetylation, exhibited strong antioxidant activity in mice. The drug induced liver injury fibrosis has a certain preventive effect.

【作者单位】：大连医科大学生物技术系;
【基金】：辽宁省教育厅科学研究一般项目(No.L2016004)
【分类号】：R575

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