聚苯乙烯纳塑料暴露对小鼠肝脏脂质代谢的影响及机制研究  

The effect and mechanism of exposure to polystyrene nanoplastics on lipid metabolism in mice liver

作　　者：张夏男[1] 孟庆涛 张洪伟[1] 王超[3] 张淑怡 陈汉清 李晓波 陈瑞 Zhang Xianan;Meng Qingtao;Zhang Hongwei;Wang Chao;Zhang Shuyi;Chen Hanqing;Li Xiaobo;Chen Rui(Yanjing Medical College,Capital Medical University,Beijing 101300,China;School of Public Health,Capital Medical University,Beijing 100069,China;China CDC Key Laboratory of Environment and Population Health/National Institute of Environmental Health,Chinese Center for Disease Control and Prevention,Beijing 100021,China)

机构地区：[1]首都医科大学燕京医学院,北京101300 [2]首都医科大学公共卫生学院,北京100069 [3]中国疾病预防控制中心环境与健康相关产品安全所,中国疾病预防控制中心环境与人群健康重点实验室,北京100021

出　　处：《中华预防医学杂志》2024年第10期1524-1533,共10页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金杰出青年基金项目(82025031);国家自然科学基金面上项目(32171370)。

摘　　要：目的探讨20 nm聚苯乙烯纳塑料(PS-NPs)暴露对小鼠肝脏脂质代谢的影响及潜在机制。方法动物实验研究,于2022年9月至2023年7月在首都医科大学公共卫生学院暴露组学平台和中国疾病预防控制中心环境与人群健康重点实验室完成。采用随机数字表法,将6~8周龄C57BL/6J雄性小鼠分为0 mg/kg(对照组)、1 mg/kg和10 mg/kg PS-NPs小鼠尾静脉暴露组,7 d后收取小鼠血清测丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)的含量。利用实时荧光定量逆转录聚合酶链反应(qRT-PCR)和空气动力辅助解吸电喷雾质谱成像(AFADESI-MSI)分析肝组织中脂肪酸酯化相关基因(Dgat1和Dgat2)、脂质转运相关基因(ApoB、Cd36、ApoE和Mttp)的mRNA水平和代谢物的空间改变。利用小动物活体光学成像系统(IVIS)进行活体和离体器官成像,组织震荡切片观察PS-NPs的荧光生物分布及强度。数据的组间比较采用t检验或单因素方差分析。结果对照组、1 mg/kg和10 mg/kg PS-NPs暴露组小鼠血清ALT含量分别为(83.97±4.58)、(91.17±13.69)和(142.43±6.09)U/L,差异有统计学意义(F=37.281,P<0.05)。Dgat1、Dgat2、ApoB、Cd36、ApoE的mRNA相对含量在对照组、1 mg/kg和10 mg/kg PS-NPs暴露组分别是(1.49±0.63,2.53±0.32,2.45±0.54)、(1.07±0.38,1.86±0.83,2.23±0.73)、(1.01±0.13,1.58±0.43,2.03±0.52)、(1.01±0.14,1.55±0.37,1.52±0.51)、(1.01±0.17,2.11±0.27,2.39±0.93),差异均有统计学意义(F=11.54、6.95、14.90、5.98、14.68,P均<0.05)。AFADESI-MSI分析发现PS-NPs暴露导致与脂质β氧化相关的戊二酰基肉碱(glutarylcarnitine)和亚油酰基肉碱(O-Linoleoylcarnitine)的含量明显下降(t=4.12和3.35,P均<0.05),而甘油三酯(TG)(m/z 921.7264,t=8.69,P<0.05;m/z 919.7114,t=3.20,P<0.05)、磷脂酸(PA)(m/z 895.7123,t=3.60,P<0.05;m/z 821.5266,t=3.36,P<0.05)、溶血磷脂胆碱(LysoPC)(m/z 560.3106,t=3.35,P<0.05;m/z 582.2953,t=6.28,P<0.05)、磷脂酰胆碱(PC)(m/z 778.5339,t=3.53,P<0.05;m/z 804.54ObjectiveTo investigate the effect and potential mechanism of exposure to 20 nm polystyrene nanoplastics(PS-NPs)on lipid metabolism in mice liver.MethodsAn animal experimental model was designed,which was completed from September 2022 to July 2023 on the exposure omics platform of the School of Public Health at Capital Medical University and the Key Laboratory of Environment and Population Health at the Chinese Center for Disease Control and Prevention.1 mg/kg and 10 mg/kg PS-NPs tail vein mice exposure models were constructed.After exposure 7 d,serum was collected to measure the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)and air flow assisted desorption electrospray ionization-mass spectrometry imaging(AFADESI-MSI)analysis were used to analyze the mRNA levels of fatty acid esterification related genes(Dgat1 and Dgat2)and lipid transport related genes(ApoB,Cd36,ApoE and Mttp)and metabolites′spatial changes in liver tissue.In vivo imaging system(IVIS)and tissue shake sections were employed to observe the fluorescence biological distribution of PS-NPs.t-test or one-way ANOVA was used to explore the difference between groups.ResultsThe serum ALT levels were(83.97±4.58),(91.17±13.69)and(142.43±6.09)U/L in the control group,1 mg/kg PS-NPs exposure group and 10 mg/kg PS-NPs exposure group respectively(F=37.281,P<0.05).The relative mRNA levels of Dgat1,Dgat2,ApoB,Cd36 and ApoE were(1.49±0.63,2.53±0.32,2.45±0.54),(1.07±0.38,1.86±0.83,2.23±0.73),(1.01±0.13,1.58±0.43,2.03±0.52),(1.01±0.14,1.55±0.37,1.52±0.51),(1.01±0.17,2.11±0.27,2.39±0.93)in these three groups respectively.The differences were statistically significant(F=11.54,6.95,14.90,5.98 and 14.68,P<0.05).AFADESI-MSI analysis found that PS-NPs exposure led to a significant decrease in the levels of glutarylcarnitine and O-Linoleoylcarnitine(t=4.12 and 3.35,P<0.05),which were associated with lipid beta oxidation.The content of triglyceride

关 键 词：聚苯乙烯纳塑料 空气动力辅助解吸电喷雾质谱成像 肝脏 脂质代谢 

分 类 号：R114[医药卫生—卫生毒理学]