蜈蚣藻多糖拮抗黄药子诱导肝毒性的实验研究  

Protection of Grateloupia filicina polysaccharide against hepatotoxicity induced by Dioscorea bulbifera L

作　　者：马神博[1] 季莉莉[2] 王顺春[2] 施松善[2] 王峥涛[1,2] 

机构地区：[1]中国药科大学生药研究室,江苏南京211198 [2]上海中医药大学中药研究所中药标准化教育部重点实验室,中药新资源与质量标准综合评价国家中医药管理局重点研究室,上海市复方中药重点实验室,上海201203

出　　处：《药学学报》2013年第8期1253-1258,共6页Acta Pharmaceutica Sinica

基　　金：教育部新世纪优秀人才计划(NCET-11-1054)

摘　　要：本文主要观察蜈蚣藻多糖(GFP)对黄药子所引起肝毒性的拮抗作用及其机制。小鼠灌胃给予不同剂量GFP,6天后给予黄药子乙酸乙酯提取物(EF),检测血清生化指标谷丙/谷草转氨酶(alanine/aspartate aminotransferase,ALT/AST)、碱性磷酸酶(alkaline phosphatase,ALP)和总胆汁酸(total bilirubin,TB),并进行肝组织病理切片观察。检测肝内还原型谷胱甘肽(glutathione,GSH)含量及GSH合成酶(glutamate cysteine ligase,GCL)活性。采用蛋白电泳(Western-blot)检测GCL催化(GCL-c)和调节(GCL-m)亚单位,血红素加氧酶(heme oxygenase-1,HO-1)的表达。结果发现:GFP(600 mg.kg 1)降低了EF诱导的ALT、AST和TB水平升高,GFP(400,600 mg.kg 1)均能降低EF增加的ALP水平。病理切片显示GFP能缓解EF诱导的肝损伤。GFP进一步升高GSH活性,逆转了EF降低的GCL活性。Western-blot结果表明:GFP逆转了EF降低的GCL-c蛋白表达,并进一步增加HO-1的表达。研究表明GFP能拮抗黄药子诱导的氧应激性肝损伤。The present study was designed to observe the protection of Grateloupiafilicina polysaccharide （GFP） against hepatotoxicity induced by Dioscorea bulbifera L in mice and its tmderlying mechanism. GFP was intragastrically （ig） given to mice at various doses. After 6 days, the mice were treated with ethyl acetate extract of Dioscorea bulbifera L （EF, ig）. Serum levels of alanine/aspartate aminotransferase （ALT/AST）, alkaline phosphatase （ALP）, total bilirubin （TB） were measured, and liver histological evaluation was conducted. Furthermore, reductions of liver glutathione （GSH） amount and glutamate cysteine ligase （GCL） activity were tested. The expressions of GCL-c, GCL-m, and HO-1 （heme oxygenase-1） in liver were observed by Western-blot. The results showed that GFP （600 mg＇kg-1） decreased EF-induced the increase of serum ALT, AST and TB, and GFP （400, 600 mg·kg^-1） inhibited EF-induced the increase of serum ALP. Liver histological evaluation showed that the liver injury induced by EF was relieved after treated with GFP. GFP further increased liver GSH amount and reversed EF-induced the decrease of GCL activity. The Western-blot result showed that GFP augmented EF-induced the increase of HO- 1, and reversed EF-induced the decrease of GCL-c. In conclusion, GFP can act against the oxidative stress liver injury induced by Dioscorea bulbifera L in mice.

关 键 词：黄药子 蜈蚣藻多糖 肝毒性 氧化应激 

分 类 号：R285[医药卫生—中药学]