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N-乙酰半胱氨酸拮抗丙烯酰胺的肝肾毒性及机制
  • ISSN号:1001-9391
  • 期刊名称:《中华劳动卫生职业病杂志》
  • 时间:0
  • 分类:R563[医药卫生—呼吸系统;医药卫生—临床医学;医药卫生—内科学]
  • 作者机构:华中科技大学同济医学院公共卫生学院教育部环境与健康重点实验室、卫生毒理学系,武汉430030
  • 相关基金:国家自然科学基金(81373042);武汉市科技局科技计划项目(2013062301010805)
中文摘要:

目的探讨丙烯酰胺(ACR)的肝肾毒性作用以及N-乙酰半胱氨酸(NAC)对ACR肝肾毒性的拮抗作用及机制。方法40只雌性SD大鼠随机分为对照组(腹腔注射生理盐水,1.5h后生理盐水灌胃)、NAc组(腹腔注射200m非异NAC,1.5h后生理盐水灌胃)、ACR组(腹腔注射生理盐水,1.5h后40mg/kgACR灌胃)和联合处理组(腹腔注射200mg/kgNAC,1.5h后40mg/kg ACR灌胃),每天染毒1次,共染毒2周。末次染毒24h后断头处死大鼠,收集血液,分离肝脏和肾脏,分别测定各组大鼠体重、脏器系数、血清生化指标,组织病理检查和检测(NF-KBp65、IKB-α及cox-2)的表达。结果从染毒第2天到染毒结束,ACR组的体重持续低于对照组,差异有统计学意义(P〈0.05);与联合处理组比较,染毒第2、3天ACR组体重降低,差异有统计学意义(P〈0.05)。ACR组肝和肾脏器系数分别为(4.159%±0.371%)和(0.764%±0.068%),明显高于对照组,差异有统计学意义(P〈O.05)。ACR组血清中ALT、AST和Cr含量分别为(77.370±16.397)U/L、(379.410±57.817)U/L和(77.812±6.391)μmol/L,与对照组及联合处理组比较,差异均无统计学意义(P〉0.05);ACR组血清中BUN含量为(7.005±1.009)mmol/L,明显高于对照组,差异有统计学意义(P〈0.05)。组织病理切片显示,ACR组肝细胞界限不清,胞核固缩,肝索结构疏松、排列紊乱,各组肾脏无明显病理改变。westem blot结果表明,ACR组肝脏中核NF.KBp65和COX-2的表达高于对照组和联合处理组,IKB-α的表达低于对照组和联合处理组,差异均有统计学意义(P〈0.05);ACR组肝脏中总NF-KBp65的表达高于对照组,差异有统计学意义(P〈0.05)。结论在该实验条件下,ACR可能通过激活NF-KB信号通路对肝脏产生毒性作用,且NAC可能通过抑制NF-KB信号通路来拮抗ACR

英文摘要:

Objective The aim of this study is to investigate hepatic and renal toxicity of acrylamide (ACR), the antagonistic effect and possible mechanism of N-acetylcysteine (NAC) on the toxicity. Methods Forty female SD rats were randomly divided into four groups. All the rats were administrated by intraperitoneal(i. p.) injection and 1.5 hours later by gavage. The controlgroup was administrated with 0.9% NaC1 by i.p. injection and gavaged with 0.9% NaC1. The NAC group was administrated with 200 mg/kg NAC by injection and gavaged with 0.9% NaC1. The ACR group was administrated with 0.9% NaC1 by injection and gavaged with 40 mg/kg ACR. The combined treatment group was administrated with 200 mg/kg NAC by i.p. injection and gavaged with 40 mg/kg ACR. The rats were administrated once a day for 2 weeks. After 24 hours of the last administration, the rats were decapitated. The blood was collected, the l~ver and kidney were separated. The body weight, organ coefficient and serum biochemical parameters were measured, and the pathological changes of the tissues were examined with a microscope. Then the expression of NF-KB p65, IKB-et and COX-2 were detected by Western blot. Results From the second day to the end of the exposure, the body weight of rats in the ACR group was statistically lower than that in the control group (P〈0.05). Compared with the combined treatment group, the body weight in the ACR group statistically decreased in the second and third days (P 〈 0.05). The liver and kidney organ coefficients in the ACR group were (4.159%±371%) and (0.764%±0.068%) respectively, which increased statistically when compared with the control group (P 〈 0.05 ). The contents of ALT, AST and Cr in the serum in the ACR group were(77.370±16.397) U/L, (379.410±57.817) U/L and (77.812±6.391) μmol/L respectively, which were not significantly different with those in the control group and the combined treatment group (P〉0.05). The content of BUN in the serum in the ACR group was ?

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期刊信息
  • 《中华劳动卫生职业病杂志》
  • 中国科技核心期刊
  • 主管单位:中国科协
  • 主办单位:中华医学会
  • 主编:
  • 地址:天津河东区华越道6号
  • 邮编:300011
  • 邮箱:cjoh1983@163.com
  • 电话:022-24333581
  • 国际标准刊号:ISSN:1001-9391
  • 国内统一刊号:ISSN:12-1094/R
  • 邮发代号:6-50
  • 获奖情况:
  • 2000年中华医学会优秀期刊银奖,2000年天津市优秀期刊奖,2001中华预防医学会优秀期刊一等奖
  • 国内外数据库收录:
  • 美国化学文摘(网络版),波兰哥白尼索引,荷兰文摘与引文数据库,美国生物医学检索系统,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2000版)
  • 被引量:16727