食品科学

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发酵轮叶党参皂苷对二乙基亚硝胺致小鼠肝细胞DNA氧化损伤的保护作用机制

俞 星1,郑春姬1,韩春姬1,2,*,姜国哲1,崔成弼2   

  1. 1.延边大学医学院预防医学教研部,吉林 延吉 133002;2.延边大学食品研究中心,吉林 延吉 133002
  • 出版日期:2013-09-15 发布日期:2013-09-27
  • 通讯作者: 韩春姬
  • 基金资助:

    科技部国际合作专项(2011DFA33470);吉林省科技厅发展计划项目(20100715)

Mechanisms Underlying the Protective Effect of Saponins Extracted from Fermented Codonopsis lanceolata against Oxidative DNA Damage Induced by Diethylnitrosamine in Liver Cells of Mice

YU Xing1,ZHENG Chun-ji1,HAN Chun-ji1,2,*,JIANG Guo-zhe1,CUI Cheng-bi2   

  1. 1. Department of Preventive Medicine, College of Medicine, Yanbian University, Yanji 133002, China;
    2. Food Research Center, Yanbian University, Yanji 133002, China
  • Online:2013-09-15 Published:2013-09-27
  • Contact: HAN Chun-ji

摘要:

目的:探讨发酵轮叶党参(FCLS)对二乙基亚硝胺(DEN)致小鼠肝细胞DNA氧化损伤的保护作用机制。方法:将50只小鼠随机分为5组:阴性对照组(灌胃蒸馏水10mL/(kg·d))、DEN组(隔日腹腔注射DEN 20mg/kg)及FCLS高、中、低剂量组(分别灌胃FCLS 200、100、50mg/(kg·d),同时隔日腹腔注射DEN 20mg/kg),连续给药6周。采用ELISA方法测定小鼠肝组织8-羟基脱氧鸟苷(8-OHdG)含量、小鼠8-羟基鸟嘌呤-DNA糖苷酶(OGG1)的活性,采用免疫组化方法测定肝细胞中的细胞色素P4502E1(CYP2E1)。结果:DEN组肝组织8-OHdG含量及CYP2E1蛋白表达明显高于阴性对照组(P<0.01),OGG1活性明显低于阴性对照组(P<0.01)。FCLS高、中剂量组肝组织8-OHdG含量明显低于DEN组(P<0.01),并随着FCLS给药剂量的增高,小鼠肝组织中8-OHdG含量也随之减少。FCLS高、中、低3个剂量组肝组织中OGG1活性明显高于DEN组,其差异显著(P<0.05或P<0.01),给药剂量与OGG1活性呈剂量-效应关系。FCLS中剂量组和高剂量组肝组织CYP2E1蛋白表达明显低于DEN组,差异显著(P<0.05或P<0.01)。结论:轮叶党参皂苷保护DEN所致DNA损伤可能与其提高抗氧化酶活性、抑制药物代谢酶及提高DNA损伤修复酶活
性有关。

关键词: 发酵, 轮叶党参, 二乙基亚硝胺, DNA损伤, 小鼠

Abstract:

Objective: To explore the mechanisms by which saponins extracted from fermented Codonopsis lanceolata
(FCLS) protect against oxidative DNA damage induced by diethylnitrosamine (DEN) in mouse liver cells and consequently
provide useful references for chemical prevention of liver cancer. Methods: Fifty mice were randomly divided into five
groups including negative control group (intragastric administration of 10 mL of distilled water per kg body weight), DEN
group (intraperitoneal injection of DEN at a dose of 20 mg/kg every other day), and high, middle and low dose FCLS groups
(intragastric administration of FCLS at doses of 200, 100, 50 mg/(kg·d), and intraperitoneal injection of DEN at a dose
of 20 mg/kg every other day). The administration period for all the treatments was 6 weeks. The contents of 8-hydroxyl
deoxyguanosine (8-OHdG) and the activity of 8-hydroxy guanine-DNA glycosylase (OGG1) in mouse hepatic tissue were
determined by ELISA, and cytochrome P4502E1 (CYP2E1) protein expression was analyzed by immunohistochemical
method. Results: The 8-OHdG content and CYP2E1 protein expression in liver tissue from the DEN group were significantly
increased when compared with those from the negative control group (P < 0.01), and OGG1 activity in the DEN group was
significantly decreased when compared with the control group (P < 0.01). The 8-OHdG content of liver tissue in the high
and middle dose FCLS groups were significantly lower than that of DEN group (P < 0.01), and increasing the FCLS dose
resulted in a lower 8-OHdG content in the FCLS treatment groups. OGG1 content in liver tissue from the DEN group was
obviously lower than that from the negative control group (P < 0.05). OGG1 content in liver tissue from the three FCLS
groups were significantly higher than that from the DEN group (P < 0.05 or P < 0.01). The dose of FCLS revealed an obvious dependent relationship with the activity of OGG1. CYP2E1 protein expression in the FCLS middle and high dose groups
were significantly lower than that from the DEN group (P < 0.05 or P < 0.01). Conclusion: The protective effect of saponins
from fermented Codonopsis lanceolata against oxidative DNA damage induced by DEN may be related to the increased activity of
antioxidant enzymes and DNA damage repair enzymes, and reduced activity of metabolic enzymes for drugs.

Key words: fermentation, Codonopsis lanceolata, diethylnitrosamine, oxidative DNA damage, mice

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