还原型谷胱甘肽对DEN诱发大鼠肝癌的预防作用  

Protection from DEN carcinogenesis by glutathion in rat hepatoma model

作　　者：石京山[1] 盛美萍[2] 李峰[2] 

机构地区：[1]遵义医学院药理学教研室 [2]上海医科大学基础医学院药理学教研室

出　　处：《遵义医学院学报》1998年第1期1-5,共5页Journal of Zunyi Medical University

摘　　要：目的：研究还原型谷胱甘肽（ＧＳＨ）对化学致癌原Ｎ－二乙基亚硝胺（ＤＥＮ）诱致雄性Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠肝癌的保护作用。方法：雄性 ＳＤ大鼠 ７５只分成 ７组，每天 ＤＥＮ ８ｍｇ／ｋｇ ｉ．ｇ 诱发大鼠肝癌模型，分别不同途径预防性给予ＧＳＨ。结果：对照组１６ｗ后大鼠的肝脏癌变率为７６．５％，伴有镜检典型的弥漫性癌结节、畸型核分裂和重度肝硬化及胆管炎，于 １２ｗ及 １６ｗ ＡＫＰ及 γ－ＧＴ明显增高；同剂量 ＤＥＮ １６ｗ伴以 ＧＳＨ １５０ｍｇ／ｋｇ、３００ｍｇ／ｋｇ、 １０００ｍｇ／ｋ（ｉｐ）及 １０００ｍｇ／ｋｇ（ ｉｇ） １６ｗ，明显降低癌变率，分别降为１１．１％、１６．７％、１６．７％及１８．２％；ＧＳＨ大剂量组大鼠未癌变，肝组织仅见少量纤维增生，ＡＫＴ及γ－ＧＴ值与正常大鼠无显著差异；ＤＥＮ诱癌１２ｗ后用ＧＳＨ治疗４ｗ对大鼠肝脏癌变率无明显防治效果。结论：早期用外源性 ＧＳＨ对 ＤＥＮ诱发大鼠肝癌有预防作用，ＤＥＮ诱发肝癌形成后用ＣＳＨ无效。Objective: The aim was to investigate the protetive effect of glutathion on hepatoma model induced by N-diethylnitrosolamine (DEN) carcinogenesis in rats. Methods: Male 75 Sprague-Dawley rats were divided into 7 groups: group (A) DEN 8mg/kg i. g. qd, 16 wk; (B), group (C), (D) & (F) groups same DEN induction + GSH 150mg/kg, 300mg/kg, 1000mg/kg 16 wk; Group (E) same DEN induction + GSH i. g. 1000mg/kg qd only 4 wk; group (F) same DEN induction + GSH i. g. qd, 16 wk; and group (G) normal rats 16 wk without medication as negative control. At 12 wk, blood samples of 5 rats in group (A) and (D) were randomly withdrawn from the tail vessel for the determination of AKP and γ-GT. At the end of 16 wk, pathological microscopic exams were taken blindly, and again 5 blood samples in each group were taken. Results: Intraperitoneal administration of GSH very significantly lowered the incidence of liver cancer down to 1 1. 1 %, 16. 7%, 16. 7 % & 18. 2% respectively in (B), (C), (D) & (F) groups, venous the very high positive incidence 76. 5 % (this experiment) and 100% (previous experiment) P all < 0. 01; liver morbidity as cirrhosis, proliferative cholangitis and fibrosis were markly protected by GSH 1000mg/kg 16 wk treatment but the short therapy (4wk) gave no curative effect. In addition, AKP & γ-GT elevation after DEN were lowered significantly by 16 wk GSH treatment. Conclusions: GSH can protect from DEN carcinogensis in rats, but gave no curative effect in the hepatoma model.

关 键 词：肝癌 谷胱甘肽 二乙基亚硝胺 预防 

分 类 号：R735.701[医药卫生—肿瘤]