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

陈芳梅; 陈隽; 谢平; 李伟; 于源华; 张晓; 韩雪荣; 于欣冉

doi:10.7524/AJE.1673-5897.20170902001

生态毒理学报

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陈芳梅, 陈隽, 谢平, 李伟, 于源华, 张晓, 韩雪荣, 于欣冉. 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. doi: 10.7524/AJE.1673-5897.20170902001

引用本文:

Chen Fangmei, Chen Jun, Xie Ping, Li Wei, Yu Yuanhua, Zhang Xiao, Han Xuerong, Yu Xinran. Quantitative study in the Process of Glutathione Detoxification of Microcystin[J]. Asian Journal of Ecotoxicology, 2018, 13(2): 99-105. doi: 10.7524/AJE.1673-5897.20170902001

Citation:

Chen Fangmei, Chen Jun, Xie Ping, Li Wei, Yu Yuanhua, Zhang Xiao, Han Xuerong, Yu Xinran. Quantitative study in the Process of Glutathione Detoxification of Microcystin[J]. Asian Journal of Ecotoxicology, 2018, 13(2): 99-105. doi: 10.7524/AJE.1673-5897.20170902001

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

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

作者简介: 陈芳梅(1992-),女,硕士研究生,研究方向为水环境毒理学,E-mail:cfm0816@163.com

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)
中图分类号: X171.5

Quantitative study in the Process of Glutathione Detoxification of Microcystin

1. 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
Fund Project:

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。
- 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
Abstract: 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 (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.
- microcystin /
- crucian carp /
- rat /
- glutathione /
- detoxification /
- LC-MS

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Citation:

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

作者简介: 陈芳梅(1992-),女,硕士研究生,研究方向为水环境毒理学,E-mail:cfm0816@163.com
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

收稿日期: 2017-09-20

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)

关键词:

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。

English Abstract

Quantitative study in the Process of Glutathione Detoxification of Microcystin

1. 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

Received Date: 2017-09-20

Fund Project:

Keywords:

Abstract: 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 (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.