生物技术通报 ›› 2023, Vol. 39 ›› Issue (3): 69-80.doi: 10.13560/j.cnki.biotech.bull.1985.2022-0793
收稿日期:
2022-06-28
出版日期:
2023-03-26
发布日期:
2023-04-10
通讯作者:
王蒙,女,博士,副研究员,研究方向:农产品质量安全;E-mail: wangm@iqstt.cn作者简介:
王昕璐,女,博士,助理研究员,研究方向:农产品质量安全;E-mail: wangxl@iqstt.cn
基金资助:
WANG Xin-lu(), WANG Meng(), ZHAI Wen-lei
Received:
2022-06-28
Published:
2023-03-26
Online:
2023-04-10
摘要:
脂质作为细胞的主要组成部分,在细胞内物质运输、信号转导、细胞凋亡等多种生命活动中发挥重要作用。脂质组学通过对生物体内的脂质进行系统分析,从而了解其相互作用以及与其他生物分子之间的作用。主要介绍了脂质组学的研究方法,包括样品前处理方法、检测方法和仪器设备以及数据分析方法。同时,综述了脂质组学技术在神经毒性、肝脏毒性、免疫毒性以及内分泌干扰毒性中的研究进展,以期为研究化合物毒性作用机制提供思路和参考。最后,提出未来应利用脂质组学技术开展不同化合物的联合毒性作用研究,通过脂质组学筛选获得相关脂质生物标志物,为联合毒性作用的风险预警和相关毒性作用机制分析提供科学依据。
王昕璐, 王蒙, 翟文磊. 脂质组学在毒理学研究中的应用[J]. 生物技术通报, 2023, 39(3): 69-80.
WANG Xin-lu, WANG Meng, ZHAI Wen-lei. Application of Lipidomics in Toxicological Studies[J]. Biotechnology Bulletin, 2023, 39(3): 69-80.
序号 No. | 样品类别 Sample type | 提取方式 Extraction method | 分析仪器 Analysis instrument | 毒性研究目标物 Toxicity research target | 参考文献 Reference |
---|---|---|---|---|---|
1 | 斑马鱼肝细胞 | 氯仿/甲醇(2:1,V/V)+0.01%丁羟甲苯 | UHPLC-Q Exactive-MS | 双酚A、双酚F、双酚3-氯-2-羟丙基醚 | [ |
2 | C57BL/6J鼠 | 甲基叔丁基醚/甲醇/水(10:3:3,V/V/V) | LC-MS/MS | 多溴联苯醚 | [ |
3 | 雄性昆明鼠血清 | 十七烷酸/甲醇(7:2,V/V) | GC-MS | 万古霉素 | [ |
4 | 太平洋白虾 | 氯仿-甲醇体系 | LC-MS/MS | 微囊藻素 | [ |
5 | PC12细胞 | 二氯甲烷/甲醇(1:2,V/V) | UHPLC-MS/MS | 多氯联苯(PCB153) | [ |
6 | 雌性ICR小鼠 | 氯仿/甲醇/水(3:4:1,V/V/V) | AP-MALDI-MS | 镉 | [ |
7 | 斑马鱼胚胎 | 氯仿/甲醇/水(2:1:1,V/V/V) | LC-QTOF-MS | 全氟己烷磺酸 | [ |
8 | 小鼠大脑皮层 | 甲醇/甲基叔丁基醚(3:10,V/V) | UHPLC-Q Exactive plus-MS | 雄黄 | [ |
9 | 小鼠脑组织 | 甲醇/甲基叔丁基醚(3:10,V/V) | LC-MS/MS | 多溴联苯醚(BDE-47) | [ |
10 | 小鼠脑组织、血液、粪便 | 甲醇/甲基叔丁基醚(1:5,V/V) | UHPLC-Q Exactive Focus-MS | 砷 | [ |
11 | 猕猴血清、脑组织 | 氯仿/甲醇/水(1:2:0.8,V/V/V) | LC-MS/MS | 七氟烷 | [ |
12 | Neuro-2a细胞 | 二氯甲烷/甲醇(1:2,V/V) | UHPLC-Q Exactive plus-MS | 吡虫啉、啶虫脒 | [ |
13 | 小鼠肝脏组织 | 氯仿/甲醇(2:1,V/V) | LC-MS/MS | 邻苯二甲酸酯 | [ |
14 | 人肝细胞 | 甲醇/甲基叔丁基醚 | UHPLC-Q Exactive-MS | 二甲基甲酰胺 | [ |
15 | HepG2细胞 | 甲醇/甲基叔丁基醚(1:3,V/V) | LC-QTOF-MS | 聚乙烯微塑料、多氯联苯 | [ |
16 | 小鼠肝脏组织 | 甲醇 | UPLC-ESI-Orbitrap-MS | 全氟己烷磺酸 | [ |
表1 不同研究中采用的脂质提取及分析方法
Table 1 Extraction and analysis methods of lipidomics in different studies
序号 No. | 样品类别 Sample type | 提取方式 Extraction method | 分析仪器 Analysis instrument | 毒性研究目标物 Toxicity research target | 参考文献 Reference |
---|---|---|---|---|---|
1 | 斑马鱼肝细胞 | 氯仿/甲醇(2:1,V/V)+0.01%丁羟甲苯 | UHPLC-Q Exactive-MS | 双酚A、双酚F、双酚3-氯-2-羟丙基醚 | [ |
2 | C57BL/6J鼠 | 甲基叔丁基醚/甲醇/水(10:3:3,V/V/V) | LC-MS/MS | 多溴联苯醚 | [ |
3 | 雄性昆明鼠血清 | 十七烷酸/甲醇(7:2,V/V) | GC-MS | 万古霉素 | [ |
4 | 太平洋白虾 | 氯仿-甲醇体系 | LC-MS/MS | 微囊藻素 | [ |
5 | PC12细胞 | 二氯甲烷/甲醇(1:2,V/V) | UHPLC-MS/MS | 多氯联苯(PCB153) | [ |
6 | 雌性ICR小鼠 | 氯仿/甲醇/水(3:4:1,V/V/V) | AP-MALDI-MS | 镉 | [ |
7 | 斑马鱼胚胎 | 氯仿/甲醇/水(2:1:1,V/V/V) | LC-QTOF-MS | 全氟己烷磺酸 | [ |
8 | 小鼠大脑皮层 | 甲醇/甲基叔丁基醚(3:10,V/V) | UHPLC-Q Exactive plus-MS | 雄黄 | [ |
9 | 小鼠脑组织 | 甲醇/甲基叔丁基醚(3:10,V/V) | LC-MS/MS | 多溴联苯醚(BDE-47) | [ |
10 | 小鼠脑组织、血液、粪便 | 甲醇/甲基叔丁基醚(1:5,V/V) | UHPLC-Q Exactive Focus-MS | 砷 | [ |
11 | 猕猴血清、脑组织 | 氯仿/甲醇/水(1:2:0.8,V/V/V) | LC-MS/MS | 七氟烷 | [ |
12 | Neuro-2a细胞 | 二氯甲烷/甲醇(1:2,V/V) | UHPLC-Q Exactive plus-MS | 吡虫啉、啶虫脒 | [ |
13 | 小鼠肝脏组织 | 氯仿/甲醇(2:1,V/V) | LC-MS/MS | 邻苯二甲酸酯 | [ |
14 | 人肝细胞 | 甲醇/甲基叔丁基醚 | UHPLC-Q Exactive-MS | 二甲基甲酰胺 | [ |
15 | HepG2细胞 | 甲醇/甲基叔丁基醚(1:3,V/V) | LC-QTOF-MS | 聚乙烯微塑料、多氯联苯 | [ |
16 | 小鼠肝脏组织 | 甲醇 | UPLC-ESI-Orbitrap-MS | 全氟己烷磺酸 | [ |
序号 No. | 研究对象 Research object | 毒性作用类型 Toxicity effect category | 差异脂质 Differential lipids | 参考文献 Reference |
---|---|---|---|---|
1 | 小鼠脑组织 | 神经毒性 | AcCa(14:0)、Cer(d18:1/21:0)、DG(16:0/16:0)等 | [ |
2 | 小鼠脑组织、血液、粪便 | 神经毒性 | PE(18:0/0:0)、PC(18:1/22:6)、PC(18:0/22:5)等 | [ |
3 | 猕猴血清、脑组织 | 神经毒性 | 16:1 LPG、18:0-20:4 PC、18:0 LPI等 | [ |
4 | Neuro-2a细胞 | 神经毒性 | MePC(33:0e)、PC(40:7)、ChE(20:4)等 | [ |
5 | 小鼠肝脏组织 | 肝脏毒性 | DG(16:0/16:0)、DG(16:0/20:4)、TG(16:0/18:2/18:2)等 | [ |
6 | 人肝细胞 | 肝脏毒性 | TG(18:1/22:6/22:6)、TG(20:2/22:6/22:6)、PE(18:0/22:6)等 | [ |
7 | HepG2细胞 | 肝脏毒性 | Cer(42:3)、HexosylCer(32:1)、SM(32:1)等 | [ |
8 | 小鼠肝脏组织 | 肝脏毒性 | LPC18:1、PI(18:0/22:5)、PC(18:0/20:2)等 | [ |
9 | ZFL细胞(斑马鱼肝脏细胞) | 肝脏毒性 | LPE(18:1)、LPC(18:1)等 | [ |
10 | 巨噬细胞 | 免疫毒性 | SM(d18:0/16:0)、Cer(d18:1/20:0)、PC(20:1/14:1)等 | [ |
11 | 人淋巴细胞 | 免疫毒性 | TG(16:0/16:1/18:2)、DG(18:2/22:6)、PC(P-14:0/24:4)等 | [ |
12 | 成年雄性大鼠 | 免疫毒性 | PGJ2、PGF2α、PGE2等 | [ |
13 | DU145前列腺癌细胞 | 内分泌干扰毒性 | PA(32:0)、LacCer(d18:1/24:0)、CL(68:2)等 | [ |
14 | MDA-MB-231细胞、雌性裸鼠 | 内分泌干扰毒性 | PC(36:1)、DG(18:1/18:2)、PE(18:0/20:4)等 | [ |
15 | MCF-7细胞 | 内分泌干扰毒性 | SM(16:0)、Lyso PC(16:0)、PC(32:1)等 | [ |
表2 以脂质组学技术开展毒理学研究筛选获得的差异脂质
Table 2 Differential lipids screened out by lipidomics in toxicology researches
序号 No. | 研究对象 Research object | 毒性作用类型 Toxicity effect category | 差异脂质 Differential lipids | 参考文献 Reference |
---|---|---|---|---|
1 | 小鼠脑组织 | 神经毒性 | AcCa(14:0)、Cer(d18:1/21:0)、DG(16:0/16:0)等 | [ |
2 | 小鼠脑组织、血液、粪便 | 神经毒性 | PE(18:0/0:0)、PC(18:1/22:6)、PC(18:0/22:5)等 | [ |
3 | 猕猴血清、脑组织 | 神经毒性 | 16:1 LPG、18:0-20:4 PC、18:0 LPI等 | [ |
4 | Neuro-2a细胞 | 神经毒性 | MePC(33:0e)、PC(40:7)、ChE(20:4)等 | [ |
5 | 小鼠肝脏组织 | 肝脏毒性 | DG(16:0/16:0)、DG(16:0/20:4)、TG(16:0/18:2/18:2)等 | [ |
6 | 人肝细胞 | 肝脏毒性 | TG(18:1/22:6/22:6)、TG(20:2/22:6/22:6)、PE(18:0/22:6)等 | [ |
7 | HepG2细胞 | 肝脏毒性 | Cer(42:3)、HexosylCer(32:1)、SM(32:1)等 | [ |
8 | 小鼠肝脏组织 | 肝脏毒性 | LPC18:1、PI(18:0/22:5)、PC(18:0/20:2)等 | [ |
9 | ZFL细胞(斑马鱼肝脏细胞) | 肝脏毒性 | LPE(18:1)、LPC(18:1)等 | [ |
10 | 巨噬细胞 | 免疫毒性 | SM(d18:0/16:0)、Cer(d18:1/20:0)、PC(20:1/14:1)等 | [ |
11 | 人淋巴细胞 | 免疫毒性 | TG(16:0/16:1/18:2)、DG(18:2/22:6)、PC(P-14:0/24:4)等 | [ |
12 | 成年雄性大鼠 | 免疫毒性 | PGJ2、PGF2α、PGE2等 | [ |
13 | DU145前列腺癌细胞 | 内分泌干扰毒性 | PA(32:0)、LacCer(d18:1/24:0)、CL(68:2)等 | [ |
14 | MDA-MB-231细胞、雌性裸鼠 | 内分泌干扰毒性 | PC(36:1)、DG(18:1/18:2)、PE(18:0/20:4)等 | [ |
15 | MCF-7细胞 | 内分泌干扰毒性 | SM(16:0)、Lyso PC(16:0)、PC(32:1)等 | [ |
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