L-苹果酸对老年小鼠PM_(2.5)暴露所致认知功能损害的影响及机制  

Effects and mechanism of L-malic acid on cognitive impairment caused by PM_(2.5) exposure in aged mice

作　　者：方侃[1] 胡怀明[1] 姜华军[1] 艾志兵[2] 周圆[1] FANG Kan;HU Huai-ming;JIANG Hua-jun;AI Zhi-bing;ZHOU Yuan(Department of Pharmacy,Taihe Hospital Affiliated to Hubei University of Medicine,Shiyan442000,China;不详)

机构地区：[1]湖北医药学院附属太和医院药学部,十堰442000 [2]湖北医药学院附属太和医院神经内科

出　　处：《医学动物防制》2021年第12期1153-1157,共5页Journal of Medical Pest Control

基　　金：2018年十堰市科学技术研究与开发立项项目(18Y27)。

摘　　要：目的探讨L-苹果酸(L-malic acid,LMA)对PM_(2.5)暴露致老年小鼠认知功能损害的影响及机制。方法选取雄性16月龄昆明小鼠120只,按随机数字表法随机分为6组:空白组、PM_(2.5)暴露组、阳性组,以及LMA低、中、高剂量组,各20只;2019年4—10月在十堰市人民南路32号采集大气PM_(2.5)样本,并制备成PM_(2.5)混悬液;采用动态气溶胶暴露系统对后5组小鼠进行染毒;染毒结束后,对LMA低、中、高剂量组分别按0.2、0.4、0.8 g/kg LMA灌胃,每天1次,连续28 d;检测各组小鼠行为学、抗氧化等指标。结果与PM_(2.5)暴露组比较,LMA中、高剂量组小鼠潜伏期(IP)明显缩短,原平台象限探索的时间(ET)明显延长、进入象限的次数(ENT)明显增多,差异均有统计学意义(t=2.728、2.533、2.826,P=0.038、0.041、0.036;t=6.363、5.441、8.356,P=0.004、0.005、0.003);与PM_(2.5)暴露组比较,LMA中、高剂量组小鼠大脑匀浆丙二醛(MDA)含量明显降低,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)含量明显提高,差异均有统计学意义(t=2.329、2.199、2.633、2.815,P=0.044、0.047、0.039、0.037;t=5.256、4.334、6.746、8.477,P=0.005、0.007、0.004、0.003);与PM_(2.5)暴露组比较,LMA中、高剂量组小鼠大脑匀浆胆碱乙酰转移酶(ChAT)活性、乙酰胆碱(ACh)、三磷酸腺苷(ATP)含量明显提高,Caspase-3活性明显降低,差异均有统计学意义(t=2.458、2.678、2.223、2.837,P=0.042、0.038、0.047、0.036;t=6.443、7.558、5.524、8.226,P=0.004、0.003、0.005、0.003)。结论LMA可以明显改善PM_(2.5)暴露致认知障碍老年小鼠的认知功能,其机制可能与抑制小鼠大脑氧化应激和细胞凋亡、提高神经元内NADPH、ATP含量和胆碱能神经功能有关。Objective To investigate the effects and mechanism of L-malic acid(LMA)on cognitive impairment caused by PM_(2.5)exposure in aged mice.Methods One hundred and twenty male Kunming-based mice aged at 16 months were randomly divided into 6 groups:blank group,PM_(2.5)exposure group,positive group,LMA groups(low,medium and high dose)with 20 mice in each group.Atmospheric PM_(2.5)samples were collected at No.32,South Renmin Road,Shiyan from April to October 2019,and PM_(2.5)suspension were prepared;dynamic aerosol exposure system was used to infect the last 5 groups of mice.The mice in LMA groups(low,medium and high dose)were administered with intragastric administration of 0.2,0.4 and 0.8 g/kg LMA once daily for 28 consecutive days after infection.The behavioral,antioxidant and other indexes between groups were detected.Results Compared with PM_(2.5)exposure group,LMA medium and high dose groups had significantly shorter incubation period(IP),significantly longer exploratory time of former platform quadrant and significantly more times of entering the original platform quadrant(ENT),the differences were statistically significant(t=2.728,2.533,2.826,P=0.038,0.041,0.036;t=6.363,5.441,8.356,P=0.004,0.005,0.003).Compared with PM_(2.5)exposure group,malondialdehyde(MDA)of brain homogenates in LMA medium and high dose groups was significantly reduced,while superoxide dismutase(SOD),activity of glutathione peroxidase(GSH-Px)and content of reduced nicotinamide adenine dinucleotide phosphate(NADPH)were significantly increased,the differences were statistically significant(t=2.329,2.199,2.633,2.815,P=0.044,0.047,0.039,0.037;t=5.256,4.334,6.746,8.477,P=0.005,0.007,0.004,0.003);compared with PM_(2.5)exposure group,the activity of choline acetyltransferase(ChAT)and contents of acetylcholine(ACh)and adenosine triphosphat(ATP)in brain homogenate of mice in the LMA medium and high dose groups were significantly increased,while caspase-3 activity was significantly decreased,the differences were statistically significant(t=2.458,2.678,

关 键 词：阿尔茨海默病 颗粒物 L-苹果酸 认知功能 氧化应激 小鼠 PM_(2.5) 

分 类 号：R122[医药卫生—环境卫生学]