基于质谱成像技术解析无机汞暴露致肾脏毒性的特征  

Investigation of Nephrotoxicity Induced by Mecury(Ⅱ)Exposure by Mass Spectrometry Imaging

作　　者：刘畅[1,2,3] 徐明 LIU Chang;XU Ming(State Key Laboratory of Environmental Chemistry and Ecotoxicology,Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing 100085,China;School of Environment,Hangzhou Institute for Advanced Study,UCAS,Hangzhou 310024,China;College of Resources and Environment,University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]中国科学院生态环境研究中心,环境化学与生态毒理学国家重点实验室,北京100085 [2]国科大杭州高等研究院环境学院,杭州310024 [3]中国科学院大学资源与环境学院,北京100049

出　　处：《分析化学》2024年第10期1553-1561,共9页Chinese Journal of Analytical Chemistry

基　　金：国家重点研发计划项目(No.2022YFC3701300);国家自然科学基金项目(Nos.22176201,22376211);中国科学院青年创新促进会项目(No.2019042)。

摘　　要：肾脏是无机汞(Hg(Ⅱ))的主要累积与损伤器官之一。然而,目前研究Hg(Ⅱ)致肾脏毒性的机制仍局限于常规的生化指标与组织病理分析方法,无法全面反映肾脏的损伤特征及其空间异质性。为了探究因Hg(Ⅱ)暴露致肾脏损伤的主要特征与作用机理,本研究采用空气动力辅助解吸电喷雾质谱成像(AFADESIMSI)技术探究了BALB/c小鼠经饮用水中Hg(Ⅱ)暴露后造成的肾脏损伤特征及典型代谢物的变化规律。组织病理分析结果显示,经3 mg/L Hg(Ⅱ)暴露28 d后,小鼠肾小球结构未见明显异常,但肾小管的管腔轻微扩张,上皮细胞扁平,间质中度扩张充血,同时出现淋巴细胞浸润,说明Hg(Ⅱ)造成了肾小管损伤,并诱发了肾小管间质炎症。与常用于肾功能评价的血生化分析法相比,质谱成像(MSI)法可更灵敏地检出Hg(Ⅱ)暴露后肾脏损伤的生物标志物变化,如肌酐。实验结果表明,与对照组相比,Hg(Ⅱ)暴露会导致皮质、髓质和肾盂区域的亚精胺、精氨酸、肌酸和肌酐水平增加,呈现出空间异质性。此外,Hg(Ⅱ)暴露还引起髓质、皮质和肾盂区域的还原型谷胱甘肽、氧化型谷胱甘肽和半胱氨酸水平升高,说明Hg(Ⅱ)可通过干扰氧化还原稳态,引起氧化应激损伤,干扰正常尿素循环,导致肾脏功能异常。MSI技术可为原位解析重金属的人体健康危害和毒性机理提供新的视角。The kidneys are the primary organ for the accumulation of inorganic mercury(Hg(Ⅱ)),which can lead to severe renal injuries.Nevertheless,the current understanding of Hg(Ⅱ)-induced nephrotoxicity is restricted to biochemical and histological methods,which might not fully identify the features of renal damages.In this study,we aimed to elucidate the characteristics and mechanisms of Hg(Ⅱ)-induced nephrotoxicity using air flow-assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI),which enabled us to examine the injury and key metabolite profile in the kidneys of mice exposed to Hg(Ⅱ)in drinking water.Histopathological analysis result showed that following a 28-day exposure of 3 mg/L Hg(Ⅱ),the glomeruli appeared unaffected,whilst the renal tubular lumen showed slight dilation,the tubular epithelial cells displayed flattening,and there was moderate interstitial congestion accompanied by lymphocyte infiltration.More importantly,the results showed that MSI offered a more sensitive detection of biomarkers linked to kidney damages,like creatinine,than blood biochemical assay frequently used for renal function assessment.This made MSI a valuable tool for toxicity assessment and disease diagnosis because it enabled the early recognition of kidney injury at the molecular level.Meanwhile,the results revealed that Hg(Ⅱ)exposure resulte d in elevation of spermidine,arginine,creatine,and creatinine level in cortex,medullaria,and renal pelvis.Additionally,Hg(Ⅱ)also led to increase of reduced glutathione,oxidized glutathione,and cysteine level in these regions.All these findings illustrated that Hg(Ⅱ)could interfere with urea cycle and caused aberrant kidney function by disrupting the redox homeostasis.In conclusion,MSI would play an important role on the health risks and toxicological mechanisms of heavy metals in the future.

关 键 词：无机汞 肾脏毒性 质谱成像 代谢物 毒性机理 

分 类 号：O657.63[理学—分析化学] R994.6[理学—化学]