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陈芳梅1,陈隽2,谢平2,李伟1,*,于源华1,张晓1,韩雪荣1,于欣冉1. 基于谷胱甘肽结合作用定量研究微囊藻毒素的解毒代谢机制[J]. 生态毒理学报, 2018, 13(2): 99-105
基于谷胱甘肽结合作用定量研究微囊藻毒素的解毒代谢机制
Quantitative study in the Process of Glutathione Detoxification of Microcystin
投稿时间:2017-09-20  修订日期:2017-11-16
DOI:10.7524/AJE.1673-5897.20170902001
中文关键词:  微囊藻毒素  鲫鱼  大鼠  谷胱甘肽  解毒机制  高效液相色谱-质谱联用
英文关键词:microcystin  crucian carp  rat  glutathione  detoxification  LC-MS
基金项目:长春理工大学青年基金项目(XQNJJ-2016-16);吉林省大学生创新创业训练计划项目(2017S065)
作者单位
陈芳梅1,陈隽2,谢平2,李伟1,*,于源华1,张晓1,韩雪荣1,于欣冉1 1. 长春理工大学生命科学技术学院长春 130022 2. 中国科学院水生生物研究所武汉 430072 
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中文摘要:
      基于谷胱甘肽(GSH)解毒作用探讨了微囊藻毒素-RR(MCRR)在不同动物肝脏和肾脏合作下的代谢机制。通过人工合成MCRR的谷胱甘肽代谢物(MCRR-GSH),腹腔注射至鲫鱼和大鼠体内,利用液相色谱串联质谱技术(LC-MS/MS)定量检测MCRR-GSH及其下游半胱氨酸代谢物(MCRR-Cys)在组织内的代谢动力学变化。在72 h的暴露实验中,实验组鲫鱼和大鼠体内均定量检测到MCRR-GSH和MCRR-Cys。MCRR-GSH在肾脏中的浓度显著高于其他组织(P< 0.05),鲫鱼和大鼠体内累积浓度分别是(0.161±0.001)和(0.116±0.005) μg g-1 DW。同样的,MCRR-Cys主要分布于鲫鱼和大鼠的肾脏组织。鲫鱼肾脏中MCRR-Cys浓度出现明显的波动,而肝脏和胆汁内的MCRR-Cys的浓度却呈现出上升的趋势;大鼠肾脏内MCRR-Cys的浓度呈缓慢下降的趋势,浓度范围为(8.899±0.817) μg g-1 DW至(3.336±0.263) μg g-1 DW。基于以上结果推测,微囊藻毒素在肝脏和肾脏合作下的解毒过程为:MC在肝脏内经GSH结合作用生成的代谢物MC-GSH随血液循环转运至肾脏,在肾脏内MC-GSH快速地转化为下游代谢物MC-Cys以促进排泄。
  
AuthorAffiliation
Chen Fangmei1, Chen Jun2, Xie Ping2, Li Wei1,*, Yu Yuanhua1, Zhang Xiao1, Han Xuerong1, Yu Xinran11. School of Life Science and Technology, Changchun University of Science and Technology, Changchun 130022, China 2. Institute of Hydrobiology, University of Chinese Academy of Sciences, Wuhan 430072, China
英文摘要:
      To study the glutathione detoxification mechanism of microcystin-RR (MCRR), the synthetic microcystin-glutathione conjugates (MCRR-GSH) were i.p. injected into crucian carp or rat. The concentrations of MCRR-GSH and its metabolite, microcystin-cysteine conjugate (MCRR-Cys), in liver, kidney and bile were analyzed by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). In the 72 h experiment, contents of MCRR-GSH and MCRR-Cys were detected in all tissues of the MCRR-GSH-treated animals. The concentrations of MCRR-GSH in kidney were obviously higher than that in liver (i>P < 0.05), and the values of MCRR-GSH concentration in crucian carp and rat were as high as (0.161±0.001) and (0.116±0.005) μg g-1 DW, respectively. Similarly, MCRR-Cys was mainly distributed in kidney. In crucian carp, concentrations of MCRR-Cys in kidney showed significant up and down while concentrations of MCRR-Cys in liver and bile showed enhanced trend; the MCRR-Cys concentration in kidney of rat was decreased from (8.899±0.817) μg g-1 DW to (3.336±0.263) μg g-1 DW. Based on these results, the detoxification process of MC after the cooperation of liver and kidney was speculated: MC conjugates with GSH in liver to form the MC-GSH conjugate, which is transferred to kidney by blood circulation system. Subsequently MC-GSH is rapidly degraded to the cysteine conjugate for excretion.
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