癌变·畸变·突变 ›› 2015, Vol. 27 ›› Issue (2): 95-100.doi: 10.3969/j.issn.1004-616x.2015.02.004

• 论著 • 上一篇    下一篇

硒对镉暴露大鼠肝脏氧化损伤的保护作用及机制研究

傅晗, 刘颖, 刘江正, 于卫华, 彭洁, 海春旭   

  1. 第四军医大学军事预防医学院军事毒理学教研室, 陕西省自由基生物学与医学重点实验室, 陕西 西安 710032
  • 收稿日期:2015-01-12 修回日期:2015-03-08 出版日期:2015-03-31 发布日期:2015-03-31
  • 通讯作者: 海春旭,E-mail:cx-hai@fmmu.edu.cn E-mail:cx-hai@fmmu.edu.cn
  • 作者简介:傅晗,E-mail:ameliebernard@sina.com。
  • 基金资助:

    国家自然科学基金(81473010)

The protective effects and underlying mechanisms of selenium administration on hepatic oxidative injury in rats with cadmium exposure

FU Han, LIU Ying, LIU Jiangzheng, YU Weihua, PENG Jie, HAI Chunxu   

  1. Department of Toxicology, School of Military Preventive Medicine, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, the Fourth Military Medical University, Xi'an 710032, Shaanxi, China
  • Received:2015-01-12 Revised:2015-03-08 Online:2015-03-31 Published:2015-03-31
  • About author:10.3969/j.issn.1004-616x.2015.02.004

摘要:

目的:探讨硒预处理对镉暴露大鼠肝脏氧化损伤的保护作用及其机制。方法:采用灌胃法建立大鼠镉暴露肝损伤模型。观察硒预处理对大鼠肝脏镉暴露相关氧化损伤的抑制作用并研究相关机制。通过检测血清中谷丙转氨酶(ALT)和谷草转氨酶(AST)活性评价大鼠肝功能;通过免疫印迹法检测Bcl-2和Bax蛋白含量并计算Bax/Bcl-2的比值来判定大鼠肝脏细胞凋亡情况;通过肝组织冰冻切片DHE探针检测肝组织活性氧(ROS)水平和试剂盒测定脂质过氧化产物丙二醛(MDA)的含量研究大鼠肝脏氧化应激状态;通过试剂盒检测肝脏组织匀浆超氧阴离子歧化酶(SOD)及分型SOD-1活力、过氧化氢酶(CAT)和谷胱甘肽过氧化氢酶(GPx)的活力,免疫印迹检测抗氧化酶SOD-1、GPx-1和CAT及抗氧化调控因子Nrf-2的蛋白水平评价大鼠肝脏抗氧化防御系统的功能。结果:与阴性对照组比较,硒预处理对镉暴露导致大鼠的血清ALT和AST升高具有显著的抑制作用(P均<0.05)。硒能抑制镉暴露导致的肝脏组织Bax/Bcl-2的升高(P<0.05),表明硒具有抑制镉导致的肝细胞凋亡的作用。硒预处理明显减缓了镉暴露导致的肝脏ROS水平和MDA水平的升高(P均<0.05),并引起抗氧化酶SOD和GPx活力的升高(P均<0.05),以及诱导核转录因子Nrf-2蛋白表达的上调(P<0.05),提示硒预处理能够有效地抑制镉暴露导致的肝脏氧化应激损伤作用。结论:硒对大鼠镉暴露导致的肝脏氧化损伤和细胞凋亡具有保护作用,其作用机制可能与增强机体抗氧化能力有关。

关键词: 氧化应激, 硒预处理, 镉暴露, 肝损伤, 抗氧化作用

Abstract:

OBJECTIVE:This study was designed to investigate the protective effects and underlying mechanisms of selenium pre-administration on hepatic oxidative injury in rats exposed to cadmium. METHODS:Rats were exposed to cadmium pre-administrated with selenium, then the inhibitory effects of selenium on liver injury, apoptosis and oxidative stress were studied. The measurements of the serum ALT and AST activities were conducted to evaluate liver function. The Bax and Bcl-2 protein levels were measured by Western Blotting and the values of Bax/Bcl-2 were obtained to evaluate hepatic apoptosis. The measurements of hepatic ROS accumulation by DHE stain and hepatic MDA level were conducted to evaluate hepatic oxidative stress. The measurements of hepatic antioxidase SOD, SOD-1, GPx activities in liver and the protein levels of SOD-1, CAT, GPx-1 and Nrf-2 were obtained to evaluate hepatic antioxidative defense ability. RESULTS:The selenium pre-administration exerted effectively protective effects on cadmium-induced liver injury, supported by the inhibition of increased ALT and AST activity. Secondly, the selenium pre-administration effectively alleviated the liver apoptosis in rats exposed to cadmium, evidenced by the decrease of Bax/Bcl-2 ratio. Thirdly, the selenium pre-administration significantly inhibited the hepatic oxidative stress in rats exposed to cadmium, illustrated by the decrease of hepatic ROS accumulation and MDA level. Finally, the enhancement of antioxidative defense ability might be the key mechanism involved in the protective effects of selenium against cadmium-induced liver injury, supported by the increase of hepatic SOD, GPx activities, and the protein expressions of SOD-1, CAT, and GPx-1 via Nrf-2 activation. CONCLUSION:Selenium pre-administration had a protective effect against hepatic oxidative injury induced by cadmium exposure and the strengthening of antioxidant defense ability via Nrf-2 activation might contribute to this protective effect.

Key words: oxidative stress, selenium pre-administration, cadmium exposure, liver injury, antioxidation

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