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潘丽1,2,魏倩1,高霞1,石影1,郑爱1,薛红丽1,李芝兰1,*. 丙烯腈诱导的氧化应激对大鼠肝脏内质网应激信号通路的影响[J]. 生态毒理学报, 2018, 13(2): 77-83
丙烯腈诱导的氧化应激对大鼠肝脏内质网应激信号通路的影响
Effects of Acrylonitrile-Induced Oxidative Damage on Endoplasmic Reticulum Stress Signaling Pathway in Rats’ Liver
投稿时间:2017-06-20  修订日期:2017-10-10
DOI:10.7524/AJE.1673-5897.20170620002
中文关键词:  丙烯腈    氧化损伤  内质网应激
英文关键词:acrylonitrile  liver  oxidative damage  endoplasmic reticulum stress
基金项目:中央高校基本科研业务费专项资金项目(lzujbky-2016-24)
作者单位
潘丽1,2,魏倩1,高霞1,石影1,郑爱1,薛红丽1,李芝兰1,* 1.兰州大学公共卫生学院兰州 730000 2.兰州市妇幼保健院兰州 730000 
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中文摘要:
      为探讨丙烯腈(acrylonitrile,ACN)诱导的大鼠肝脏氧化损伤对内质网应激(endoplasmic reticulum stress,ERS)信号通路的影响,我们将50只SPF级成年雄性SD大鼠按体重随机分为5组,每组10只。各组分别以12.5、25.0、50.0 mg kg-1 ACN灌胃染毒,N-乙酰半胱氨酸(N-acetylcysteine,NAC)干预组先用300.0 mg kg-1 NAC灌胃30 min后再灌50.0 mg kg-1 ACN,对照组以0.5 mL (100 g)-1的玉米油灌胃,1 次 天-1,6 天 周-1,共计13周。染毒结束后,检测肝脏组织氧化还原酶活力及丙二醛(malondialdehyde,MDA)含量,GRP78、CHOP及caspase-12 mRNA及蛋白表达水平。结果显示:低、中ACN组大鼠肝脏GSH含量显著低于对照组(P<0.05);低ACN组大鼠肝脏GSH-Px活力、SOD活力及MDA含量均显著高于对照组(P<0.05);中、高ACN组大鼠肝脏CAT活力明显低于对照组(P<0.05)。NAC干预后可逆转ACN诱导的大鼠肝脏GSH含量、MDA含量及SOD活力的变化。RT-PCR结果显示,高ACN组大鼠肝脏GRP78、CHOP、caspase-12 mRNA表达水平与对照组比较均升高(P<0.05)。NAC干预后,CHOP、caspase-12 mRNA表达水平与高ACN组比较均降低(P<0.05)。Western Blot结果显示,高ACN组大鼠肝脏GRP78、CHOP、caspase-12蛋白表达水平与对照组比较均升高(P<0.05),NAC干预后可逆转以上作用。结果表明,ACN慢性染毒对大鼠肝脏的氧化损伤可激活ERS信号通路,NAC可减轻氧化损伤的程度而阻断ERS信号通路,这可能是ACN产生肝脏毒性的机制之一。
  
AuthorAffiliation
Pan Li1,2,Wei Qian1,Gao Xia1,Shi Ying1,Zheng Ai1,Xue Hongli1,Li Zhilan1,*1. School of Public Health,Lanzhou University,Lanzhou 730000,China 2. Lanzhou Maternal and Child Health Hospital,Lanzhou 730000,China
英文摘要:
      In order to study the effects of acrylonitrile (ACN)-induced oxidative damage on endoplasmic reticulum stress (ERS) signaling pathways in rat liver, 50 healthy adult male SD rats were randomly divided into 5 groups, 10 rats in each group, according to the body weight. The rats’ groups were treated with 0, 12.5, 25, 50.0 mg kg-1 ACN via gavage, respectively. NAC group were treated by intragastric administration of 300.0 mg kg-1 NAC after 30 min of reperfusion 50.0 mg kg-1 ACN, 1 time per day, 6 days per week for 13 weeks. The levels of GSH and MDA, the activity of SOD, GSH-Px, CAT in liver tissue were measured by spectrophotometry method. The mRNA and protein expressing levels of ERS-related GRP78, CHOP and caspase-12 were detected by RT-PCR and Western Blot. The results showed that the levels of GSH in low and middle ACN group were significantly decreased compared to control group. The activity of GSH-Px and SOD, the levels of MDA in low dose group was significantly increased compared to control group. CAT activity in middle and high dose groups were significantly decreased in comparison with the control group. Compared with high ACN group, GSH levels was significantly increased in NAC intervention group, and also MDA levels and SOD activity were significantly decreased. GRP78, CHOP and caspase-12 in high ACN group showed significant higher mRNA levels than that in the control group. The expression of CHOP and caspase-12 mRNA in NAC group were significantly lower than that in high ACN group. Western Blot showed that the expression levels of GRP78, CHOP and caspase-12 protein in high ACN group were significantly higher than that in control group. The expression levels of GRP78, CHOP, and caspase-12 protein in NAC group were lower than that in high ACN group. Our study indicated that exposure to ACN could induce oxidative damage on rats’ liver, and then activate ERS signaling pathway. NAC could reduce the degree of oxidative damage and antagonize the ERS signaling pathway. Further study is needed to find the mechanism of this oxidative damage inducted by ACN on ERS signaling pathway.
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