DEHP和高脂暴露对小鼠脑组织氨基酸类神经递质、神经元的影响  

Effects of DEHP and high-fat on amino acid neurotransmitters and neurons in mice brain tissues

作　　者：郑刘根 单姗 程东[2] 李慧[2] 姚文环[2] 赵秀兰[1] 张天亮[3] ZHENG Liu-gen;SHAN Shan;CHENG Dong;LI Hui;YAO Wen-huan;ZHAO Xiu-Lan;ZHANG Tian-Liang(Department of Toricology and Nutrition,School of Public Health,Shandong University,Jinan,Shandong 250012,China;Institute of Health Inspection and Testing,Shandong Center for Disease Control and Prevention;Shandong Center for Disease Control and Prevention)

机构地区：[1]山东大学公共卫生学院毒理与营养学系,山东济南250012 [2]山东省疾病预防控制中心卫生检验检测所 [3]山东省疾病预防控制中心

出　　处：《预防医学论坛》2023年第2期146-151,共6页Preventive Medicine Tribune

基　　金：国家自然科学基金资助项目(82073587,81872654);山东省重点研发计划(重大科技创新工程)项目(2020CXGC10604)。

摘　　要：目的观察长期低剂量邻苯二甲酸二(2-乙基己基)酯[di(2-ethylhexyl)phthalate,DEHP]暴露及高脂喂养对小鼠脑组织氨基酸类神经递质和神经元的影响。方法选择体质量16~18 g SPF级雌性C57BL/6J小鼠,适应性喂养1周,随机分为对照组(Con组)、DEHP组(DEHP组)、高脂组(HFD组)、DEHP暴露联合HFD喂养组(HFD+DEHP组)。DEHP组和HFD+DEHP组小鼠经口给予50μg/kg DEHP,Con组、HFD组小鼠给予等体积溶剂,Con组、DEHP小鼠喂饲普通维持饲料,HFD组、HFD+DEHP组小鼠喂饲高脂饲料。第24周末,每组随机取8只小鼠脱臼处死,取脑组织制备匀浆,并采用高效液相色谱法检测脑组织氨基酸类神经递质水平;每组剩余4只小鼠经体内灌注固定,制备大脑冰冻切片,采用尼氏染色观察神经元的变化。结果HFD+DEHP组大脑皮层GABA高于Con组、DEHP组,HFD组、HFD+DEHP组Glu/GABA低于Con组(P<0.05);各组其他指标比较差异无统计学意义(P>0.05)。各组中脑中氨基酸类神经递质水平比较差异无统计学意义(P>0.05)。DEHP组、HFD组、HFD+DEHP组小脑Gly均高于Con组,HFD+DEHP组GABA高于Con组、DEHP组、HFD组(P<0.05);各组其他指标比较差异无统计学意义(P>0.05)。与Con组相比,DEHP组、HFD组及HFD+DEHP组小鼠大脑神经元中尼氏体颜色变淡、着色颗粒稀疏,以HFD+DEHP组最为明显。结论DEHP长期暴露和高脂饮食可破坏小鼠脑内氨基酸类神经递质的内稳态,导致神经元损伤。Objective To observe the effects of long-term low-dose di(2-ethylhexyl)phthalate(DEHP)exposure and high-fat diet(HFD)on amino acid neurotransmitters and neurons in the brain of mice.Methods Female C57BL/6J mice weighing 16-18 g were housed at the SPF grade animal center for 1 week and randomly divided into control group(Con),DEHP group(DEHP),HFD group(HFD),and DEHP-HFD co-exposed group(HFD+DEHP).Mice of DEHP and HFD+DEHP group were orally exposed to 50μg/kg DEHP,while mice of other groups were gavaged with equal volume of solvent.At the end of 24th weeks,8 mice was randomly selected from each group and sacrificed by dislocation,brain tissues were collected,homogenized and followed by detection of amino acid neurotransmitters by high performance liquid chromatography(HPLC).The 4 remaining mice in each group were fixed via transcardiac perfusion with 4%paraformaldehyde,the brains were taken out for frozen sections.Then,the slices were performed Nissl staining to observe the changes of neuronal Nissl bodies.Results The brain cortex levels of GABA in mice co-treated DEHP and HFD were significantly higher than those of mice in Con and DEHP groups(P<0.05),the brain cortex Glu/GABA ratio of mice in the HFD and HFD+DEHP groups were lower than Con group(P<0.05);there was no statistically significant difference in the comparison of other indicators among different groups(P>0.05).The levels of all the amino acid neurotransmitters kept unchangeable in midbrain of mice among different groups.The cerebellar levels of Gly were significantly increased in the DEHP,HFD and HFD+DEHP treated mice compared with the control mice(P<0.05),and cerebellar GABA levels of mice from HFD+DEHP group were obviously higher than those of mice in Con,DEHP and HFD groups(P<0.05);Other indicators had no significantly difference(P>0.05).The thionine staining showed that HFD and DEHP treatment led to lighter staining Nissl body,reduced density of colored granules,with the HFD+DEHP treated mice being the most pronounced.Conclusion Long-term exposure t

关 键 词：邻苯二甲酸二乙基己酯 高脂饮食 氨基酸类神经递质 神经毒性 脑组织 

分 类 号：R135.1[医药卫生—劳动卫生]