不同粒径可吸入颗粒物全身暴露对老年小鼠认知功能的影响及其机制研究  

Effects and its mechanism of systemic exposure to inhalable particles with different particle sizes on cognitive function in elderly 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,Department of Neurology,Shiyan 442000,Hubei,CHINA;Department of Pharmacy,Taihe Hospital Affiliated to Hubei University of Medicine,Shiyan 442000,Hubei,CHINA)

机构地区：[1]湖北医药学院附属太和医院药学部,湖北十堰442000 [2]湖北医药学院附属太和医院神经内科,湖北十堰442000

出　　处：《海南医学》2021年第3期273-277,共5页Hainan Medical Journal

基　　金：2018年湖北省十堰市科学技术研究与开发立项项目(编号:18Y19)。

摘　　要：目的观察不同粒径可吸入颗粒物(PM)全身暴露对老年小鼠认知功能的影响,并探讨其作用机制。方法选取雄性16个月龄昆明小鼠100只,按随机数表法分为正常对照组、生理盐水组、粗颗粒物(PM10)染毒组、细颗粒物(PM2.5)染毒组、超细颗粒物(UFPs)染毒组,每组20只。2018年12月至2019年6月在十堰市人民南路32号采集大气PM10、PM2.5、UFPs样本,并制备成PM10、PM2.5、UFPs悬液。采用动态气溶胶染毒暴露系统对PM10染毒组、PM2.5染毒组、UFPs染毒组小鼠实施全身暴露染毒;控制舱PM浓度稳定在(1500±10)μg/m^3,每天吸入12 h,连续4周;生理盐水组小鼠雾化吸入生理盐水,正常对照组不做任何处理。染毒结束后,测试各组小鼠行为学的潜伏期(IP)、进入原平台象限次数(ENT)、在原平台象限探查时间(PT),并检测各组小鼠大脑匀浆中肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素-1β(IL-1β)、核转录因子κB(NF-κB)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、乙酰胆碱(ACh)、胆碱乙酰转移酶(ChAT)及含半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)的表达水平。结果①与正常对照组小鼠行为学IP、ENT、PT比较,生理盐水组、PM10染毒组小鼠的IP、ENT、PT变化不明显,差异均无统计学意义(P>0.05),但PM2.5染毒组小鼠的IP明显延长、ENT明显减少、PT明显缩短,差异均有统计学意义(P<0.05);而UFPs染毒组染毒组IP、ENT、PT变化更明显,差异均有显著统计学意义(P<0.01)。②与正常对照组小鼠大脑匀浆TNF-α、IL-6、IL-1β、NF-κB表达水平比较,生理盐水组、PM10染毒组小鼠的TNF-α、IL-6、IL-1β、NF-κB水平变化不明显,差异均无统计学意义(P>0.05),但PM2.5染毒组小鼠的TNF-α、IL-6、IL-1β、NF-κB水平明显升高,差异均有统计学意义(P<0.05);而UFPs染毒组小鼠的TNF-α、IL-6、IL-1β、NF-κB表达水平升高更明显,差异均有显著统计学意�Objective To observe the effect of systemic exposure of inhalable particulate matter(PM)with different particle sizes on cognitive function in aged mice and to explore its mechanism.Methods One hundred male kunming mice aged 16 months were selected and randomly divided into 5 groups according to the numerical table method:normal control group,normal saline group,coarse particulate matter(PM10)exposure group,fine particulate matter(PM2.5)exposure group,and ultra-fine particulate matter(UFPs)exposure group,with 20 mice in each group.From December 2018 to June 2019,air PM10,PM2.5,and UFPs samples were collected at No 32,Renmin South Road,Shiyan City,and PM10,PM2.5,and UFPs suspensions were prepared.The mice in PM10 poisoning group,PM2.5 poisoning group,and UFPs poisoning group were exposed to the whole body by dynamic aerosol exposure system.The PM concentration in the control chamber was stable at(1500±10)μg/m^3,and was inhaled for 12 hours every day for 4 weeks.Mice in normal saline group inhaled normal saline,while normal control group received no treatment.After the end of the infection,the incubation period(IP),the number of times of entering the original platform quadrant(ENT),and probe time in the original platform quadrant(PT)of mice in each group were tested,and the expression level of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β),nuclear transcription factorκB(NF-κB),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),acetylcholine(ACh),choline acetyltransferase(ChAT),and aspartic acid proteolytic enzyme-3 containing cysteine(Caspase-3)were detected in brain homogenates.Results①Compared with those of the normal control group,there were no significant changes in IP,ENT and PT in the saline group and the PM10 exposure group(P>0.05);in the PM2.5 exposure group,IP was significantly extended,ENT was significantly reduced,PT was significantly shortened(P>0.05);changes in IP,ENT,and PT of the UFPs exposure group were more significant(P<0.01).②Compar

关 键 词：阿尔茨海默病 昆明小鼠 可吸入颗粒物 认知功能 氧化应激 炎症反应 

分 类 号：R-332[医药卫生]