慢性镉暴露小鼠的肝脂质组学研究

郝蓉蓉; 李玲; 田丽; 谢佳; 陈梦妍; 余争平; 皮会丰

doi:10.11659/jjssx.03E023098

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慢性镉暴露小鼠的肝脂质组学研究

基础研究 | 更新时间：2024-04-01

- 慢性镉暴露小鼠的肝脂质组学研究
- Hepatic lipidomics study in chronic cadmium-exposed mice
- 局解手术学杂志 2024年33卷第3期页码：194-199
- 作者机构：
  
  陆军军医大学军事预防医学系军队劳动卫生学教研室/教育部电磁辐射医学防护重点实验室，重庆 400038
- 作者简介：
  
  皮会丰，E-mail：pihuifeng2010@163.com
- 基金信息：
  
  国家自然科学基金面上项目(82173473);国家自然科学基金青年基金项目(81703267);重庆英才包干制项目(cstc2024ycjh-bgzxm0069)
- DOI：10.11659/jjssx.03E023098
  中图分类号： R995
- 纸质出版日期：2024-03-25，
  
  收稿日期：2023-03-15，
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郝蓉蓉,李玲,田丽等.慢性镉暴露小鼠的肝脂质组学研究[J].局解手术学杂志,2024,33(03):194-199.

HAO Rong-rong,LI Ling,TIAN Li,et al.Hepatic lipidomics study in chronic cadmium-exposed mice[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(03):194-199.
郝蓉蓉,李玲,田丽等.慢性镉暴露小鼠的肝脂质组学研究[J].局解手术学杂志,2024,33(03):194-199. DOI： 10.11659/jjssx.03E023098.

HAO Rong-rong,LI Ling,TIAN Li,et al.Hepatic lipidomics study in chronic cadmium-exposed mice[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(03):194-199. DOI： 10.11659/jjssx.03E023098.

摘要

目的

研究慢性镉暴露小鼠肝脂质组学的改变，并筛选出具有显著差异的脂质亚类、脂质分子和富集的代谢通路。

方法

选用12只SPF级雄性C57BL/6J小鼠（8周龄），随机分成对照组（正常水喂养）和实验组[镉水（0.6 mg /L CdCl

）喂养]，每组6只。在镉暴露6个月后处死小鼠，即刻摘取新鲜的肝组织。对肝组织行脂质油红O染色和脂质组学分析。

结果

与对照组相比，实验组小鼠肝组织脂质油红O染色未出现红色。通过脂质组学筛选到17种具有显著差异的脂质亚类，144个具有显著差异的脂质分子。将具有显著差异的脂质分子通过KEGG富集得到以下通路：甘油磷脂代谢、亚油酸代谢、α-亚麻酸代谢、糖基磷脂酰肌醇生物合成、甘油脂代谢、花生四烯酸代谢。

结论

本研究通过建立慢性镉暴露模型，揭示了慢性镉暴露会诱导小鼠肝中脂质亚类和脂质代谢物的紊乱，为了解慢性镉暴露导致的非酒精性脂肪性肝病提供依据。

Abstract

Objective

To study the change of lipidomics in chronic cadmium-exposed mice，thereby screening out lipid subclasses，lipid molecules and enriched metabolic pathways with significant differences.

Methods

Twelve SPF male C57BL/6J mice （8 weeks old） were randomly divided into the control group （normal water feeding） and the experimental group ［cadmium water （0.6 mg/L of CdCl

） feeding］，with 6 mice in each group.Mice were sacrificed after 6 months of cadmium exposure，and fresh liver tissues were collected immediately.Lipid oil red O staining and lipidomics analysis were performed on liver tissue.

Results

Compared with the control group，the liver tissue of mice in the experimental group did not appear red after lipid oil red O staining.Seventeen lipid subclasses with significant differences and 144 lipid molecules with significant differences were screened out by lipidomics.These lipid molecules with significant differences were enriched in glycerophospholipid metabolism，linoleic acid metabolism，alpha-linolenic acid metabolism，glycosylphosphatidylinositol biosynthesis，glycerolipid metabolism and arachidonic acid metabolism by KEGG.

Conclusion

This study reveals that chronic cadmium exposure can induce the disorder of lipid subclasses and lipid metabolites in the liver of mice，which provides a basis for understanding the non-alcoholic fatty liver disease caused by chronic cadmium exposure.

关键词

慢性镉暴露肝脂质组学非酒精性脂肪性肝病

Keywords

chronic cadmium exposureliverlipidomicsnon-alcoholic fatty liver disease

references

Clemens S.Toxic metal accumulation，responses to exposure and mechanisms of tolerance in plants［J］.Biochimie，2006，88（11）：1707-1719.doi：10.1016/j.biochi.2006.07.003http://dx.doi.org/10.1016/j.biochi.2006.07.003.

Souza-Arroyo V，Fabián JJ，Bucio-Ortiz L，et al.The mechanism of the cadmium-induced toxicity and cellular response in the liver［J］.Toxicology，2022，480：153339.doi：10.1016/j.tox.2022.153339http://dx.doi.org/10.1016/j.tox.2022.153339.

Szántó M，Gupte R，Kraus W，et al.PARPs in lipid metabolism and related diseases［J］.Prog Lipid Res，2021，84：101117.doi：10.1016/j.plipres.2021.101117http://dx.doi.org/10.1016/j.plipres.2021.101117.

Zhu Y，Zhao Y，Chai X，et al.Chronic exposure to low-dose cadmium facilitated nonalcoholic steatohepatitisin mice by suppressing fatty acid desaturation［J］.Ecotoxicol Environ Saf，2022，233：113306.doi：10.1016/j.ecoenv.2022.113306http://dx.doi.org/10.1016/j.ecoenv.2022.113306.

He X，Gao J，Hou H，et al.Inhibition of mitochondrial fatty acid oxidation contributes to development of nonalcoholic fatty liver disease induced by environmental cadmium exposure［J］.Environ Sci Technol，2019，53（23）：13992-14000.doi：10.1021/acs.est.9b05131http://dx.doi.org/10.1021/acs.est.9b05131.

李自发，张浩，任萌，等.槲皮素对镉致小鼠肝脏脂质代谢紊乱模型的保护效应［J］.实验动物与比较医学，2021，41（4）：305-312.doi：10.12300/j.issn.1674-5817.2021.007http://dx.doi.org/10.12300/j.issn.1674-5817.2021.007.

殷艳.基于液相色谱-高分辨质谱技术的食品脂质组学分析［J］.检验检疫学刊，2020，30（2）：87-89.

Taguchi R，Ishikawa M.Precise and global identification of phospholipid molecular species by an Orbitrap mass spectrometer and automated search engine Lipid Search［J］.J Chromatogr A，2010，1217（25）：4229-4239.doi：10.1016/j.chroma.2010.04.034http://dx.doi.org/10.1016/j.chroma.2010.04.034.

Wang M，Chen Z，Song W，et al.A review on cadmium exposure in the population and intervention strategies against cadmium toxicity［J］.Bull Environ Contam Toxicol，2021，106（1）：65-74.doi：10.1007/s00128-020-03088-1http://dx.doi.org/10.1007/s00128-020-03088-1.

Hao R，Xiao H，Wang H，et al.Transcriptomics integrated with metabolomics unravels the interweaving of inflammatory response and 1-stearoyl-2-arachidonoyl-sn-glycerol metabolic disorder in chronic cadmium exposure-induced hepatotoxicity［J］.Environ Toxicol Pharmacol，2023，101：104172.doi：10.1016/j.etap.2023.104172http://dx.doi.org/10.1016/j.etap.2023.104172.

罗燕，邓平，陈梦研，等.慢性镉暴露小鼠肝、肾、脑组织镉分布情况和肾毒性研究［J］.局解手术学杂志，2022，31（5）：373-378.doi：10.11659/jjssx.11E021135http://dx.doi.org/10.11659/jjssx.11E021135.

Zhang L，Wang H，Abel G，et al.The effects of gene-environment interactions between cadmium exposure and apolipoprotein E4 on memory in a mouse model of Alzheimer´s disease［J］.Toxicol Sci，2020，173（1）：189-201.doi：10.1093/toxsci/kfz218http://dx.doi.org/10.1093/toxsci/kfz218.

Go YM，Sutliff RL，Chandler JD，et al.Low-dose cadmium causes metabolic and genetic dysregulation associated with fatty liver disease in mice［J］.Toxicol Sci，2015，147（2）：524-534.doi：10.1093/toxsci/kfv149http://dx.doi.org/10.1093/toxsci/kfv149.

Mezynska M，Brzóska MM.Environmental exposure to cadmium：a risk for health of the general population in industrialized countries and preventive strategies［J］.Environ Sci Pollut Res Int，2018，25（4）：3211-3232.doi：10.1007/s11356-017-0827-zhttp://dx.doi.org/10.1007/s11356-017-0827-z.

Deng P，Li J，Lu Y，et al.Chronic cadmium exposure triggered ferroptosis by perturbing the STEAP3-mediated glutathione redox balance linked to altered metabolomic signatures in humans［J］.Sci Total Environ，2023，905：167039.doi：10.1016/j.scitotenv.2023. 167039http://dx.doi.org/10.1016/j.scitotenv.2023.167039.

王爰民，刘丽华，刘汉俊.甘油三脂和胆固醇浓度对血浆粘度的影响［J］.中国血液流变学杂志，1993（2）：4-5.

Duran EK，Aday AW，Cook NR，et al.Triglyceride-rich lipoprotein cholesterol，small dense LDL cholesterol，and incident cardiovascular disease［J］.J Am CollCardiol，2020，75（17）：2122-2135.doi：10.1016/j.jacc.2020.02.059http://dx.doi.org/10.1016/j.jacc.2020.02.059.

Budoff M.Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease［J］.Am J Cardiol，2016，118（1）：138-145.doi：10.1016/j.amjcard.2016.04.004http://dx.doi.org/10.1016/j.amjcard.2016.04.004.

Alves-Bezerra M，Cohen DE.Triglyceride metabolism in the liver［J］.Compr Physiol，2017，8（1）：1-8.doi：10.1002/cphy.c170012http://dx.doi.org/10.1002/cphy.c170012.

毛逸霖，周俊，陈凯，等.甘油二酯的代谢机制及营养功能特性研究进展［J］.中国油脂，2023，48（11）：80-89.doi：10.19902/j.cnki.zgyz.1003-7969.220450http://dx.doi.org/10.19902/j.cnki.zgyz.1003-7969.220450.

Lyu K，Zhang Y，Zhang D，et al.A membrane-bound diacylglycerol species induces PKCϵ-mediated hepatic insulin resistance［J］.Cell Metab，2020，32（4）：654-664.e5.doi：10.1016/j.cmet.2020. 08.001http://dx.doi.org/10.1016/j.cmet.2020.08.001.

Ling J，Chaba T，Zhu L，et al.Hepatic ratio of phosphatidylcholine to phosphatidylethanolamine predicts survival after partial hepatectomy in mice［J］.Hepatology，2012，55（4）：1094-1102.doi：10.1002/hep.24782http://dx.doi.org/10.1002/hep.24782.

Li Z，Agellon LB，Allen TM，et al.The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis［J］.Cell Metab，2006，3（5）：321-331.doi：10.1016/j.cmet.2006.03.007http://dx.doi.org/10.1016/j.cmet.2006.03.007.

蒲云峰，张伟敏，钟耕.神经酰胺功能和应用［J］.粮食与油脂，2005（7）：14-16.doi：10.3969/j.issn.1008-9578.2005.07.004http://dx.doi.org/10.3969/j.issn.1008-9578.2005.07.004.

Chaurasia B，Summers SA.Ceramides-lipotoxic inducers of metabolic disorders：（trends in endocrinology and metabolism 26，538-550； 2015）［J］.Trends Endocrinol Metab，2018，29（1）：66-67.doi：10.1016/j.tem.2017.09.005http://dx.doi.org/10.1016/j.tem.2017.09.005.

Choi RH，Tatum SM，Symons JD，et al.Ceramides and other sphingolipids as drivers of cardiovascular disease［J］.Nat Rev Cardiol，2021，18（10）：701-711.doi：10.1038/s41569-021-00536-1http://dx.doi.org/10.1038/s41569-021-00536-1.

Chaurasia B，Summers SA.Ceramides-lipotoxic inducers of metabolic disorders［J］.Trends Endocrinol Metab，2015，26（10）：538-550.doi：10.1016/j.tem.2015.07.006http://dx.doi.org/10.1016/j.tem.2015.07.006.

Xia JY，Holland WL，Kusminski C，et al.Targeted induction of ceramide degradation leads to improved systemic metabolism and reduced hepatic steatosis［J］.Cell Meta，2015，22（2）：266-278.doi：10.1016/j.cmet.2015.06.007http://dx.doi.org/10.1016/j.cmet.2015.06.007.

Paul B，Lewinska M，Andersen JB.Lipid alterations in chronic liver disease and liver cancer［J］.JHEP Rep，2022，4（6）：100479.doi：10.1016/j.jhepr.2022.100479http://dx.doi.org/10.1016/j.jhepr.2022.100479.

Naughton SS，Mathai ML，Hryciw D，et al.Linoleic acid and the pathogenesis of obesity［J］.Prostaglandins Other Lipid Mediat，2016，125：90-99.doi：10.1016/j.prostaglandins.2016.06.003http://dx.doi.org/10.1016/j.prostaglandins.2016.06.003.

Maciejewska D，Drozd A，Skonieczna-Żydecka K，et al.Eicosanoids in nonalcoholic fatty liver disease （NAFLD） progression.Do serum eicosanoids profile correspond with liver eicosanoids content during NAFLD development and progression［J］.Molecules，2020，25（9）：2026.doi：10.3390/molecules25092026http://dx.doi.org/10.3390/molecules25092026.

Sonnweber T，Pizzini A，Nairz M，et al.Arachidonic acid metabolites in cardiovascular and metabolic diseases［J］.Int J Mol Sci，2018，19（11）：3285.doi：10.3390/ijms19113285http://dx.doi.org/10.3390/ijms19113285.

Prentki M，Madiraju SR.Glycerolipid metabolism and signaling in health and disease［J］.Endocr Rev，2008，29（6）：647-676.doi：10.1210/er.2008-0007http://dx.doi.org/10.1210/er.2008-0007.

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慢性镉暴露小鼠肝、肾、脑组织镉分布情况和肾毒性研究