D-氨基酸氧化酶在砷致仔鼠学习记忆损伤中作用的研究  

Effects of D-amino acid oxidase on learning and memory impairment in offspring mice induced by arsenic

作　　者：牛泽华 李金蕊 张桐 葛莉莉 黄睿 吴玉刚 王艳 NIU Zehua;LI Jinrui;ZHANG Tong;GE Lili;HUANG Rui;WU Yugang;WANG Yan(Postgraduate Majoring in Occupational and Environmental Health,School of Public Health,Shenyang Medical College,Shenyang 110034,China;Undergraduate Majoring in Preventive Medicine;Department of Occupational Health and Occupational Medicine)

机构地区：[1]沈阳医学院公共卫生学院,辽宁沈阳110034 [2]沈阳医学院,辽宁沈阳110034 [3]沈阳医学院公共卫生学院职业卫生与职业医学教研室,辽宁沈阳110034

出　　处：《沈阳医学院学报》2023年第5期454-457,共4页Journal of Shenyang Medical College

基　　金：国家自然科学基金项目(No.81872570);辽宁省自然科学基金项目(No.2021-MS-347);沈阳医学院大学生创新创业项目(No.20229023)。

摘　　要：目的:探讨D-氨基酸氧化酶(DAAO)在砷所致仔鼠学习记忆损伤中的作用。方法:建立仔鼠砷暴露模型(60 mg/L NaAsO_(2)),出生后6周的仔鼠腹腔注射DAAO的抑制剂6-氯苯并[d]异恶唑-3-醇(CBIO)(30 mg/kg)干预2周,Real-time RT-PCR测定DAAO、突触素(SYP)和突触后致密物95(PSD95)mRNA表达水平,UHPLC-MS/MS法测定D-丝氨酸和L-丝氨酸水平。结果:与对照组比较,NaAsO_(2)组仔鼠海马DAAO mRNA表达水平升高而SYP和PSD95 mRNA表达水平下降(P<0.05),D-丝氨酸和L-丝氨酸水平下降(P<0.05);与NaAsO_(2)组比较,NaAsO_(2)+CBIO组仔鼠海马DAAO mRNA表达水平下降而SYP mRNA表达水平升高(P<0.05),D-丝氨酸水平升高(P<0.05)。结论:砷暴露可使仔鼠海马D-丝氨酸水平降低和DAAO转录水平升高,抑制DAAO水平可使D-丝氨酸和突触相关蛋白SYP水平升高,从而可能改善砷暴露所致的仔鼠学习记忆损害。Objective:To investigate the effects of D-amino acid oxidase(DAAO)on learning and memory impairment in offspring mice induced by arsenic.Methods:The model of offspring mice exposed to arsenite(60 mg/L NaAsO_(2))was established.The mice model of exposure to arsenic during pregnancy was induced using 60 mg/L NaAsO_(2).At 6 weeks after birth,the DAAO inhibitor CBIO was given intraperitoneally for 2 weeks.The mRNA levels of DAAO,synaptophysin(SYP)and postsynaptic density 95(PSD95)were detected by Real-time RT-PCR,the levels of D-serine and L-serine were determined by UHPLC-MS/MS.Results:Compared with the control group,the level of DAAO mRNA increased,the levels of SYP and PSD95 mRNA decreased in the hippocampus of mice,and D-serine and L-serine levels significantly decreased in the NaAsO_(2) group(P<0.05).Compared with the NaAsO_(2) group,the level of DAAO mRNA decreased,the level of SYP mRNA increased significantly in the hippocampus of mice,and D-serine increased significantly in the NaAsO_(2)+CBIO group(P<0.05).Conclusions:Arsenic exposure can decrease the levels of D-serine and increase the transcription levels of DAAO in the hippocampus of offspring mice.And inhibition of DAAO can increase the levels of D-serine and SYP,which may improve the learning and memory impairment in offspring mice induced by arsenic exposure.

关 键 词：砷 D-丝氨酸 D-氨基酸氧化酶 学习记忆 

分 类 号：R994.6[医药卫生—毒理学]