L-苹果酸对老年小鼠铝暴露所致学习记忆损害的影响及机制  

Effect and its mechanism of L-malic acid on learning and memory impairment caused by aluminum exposure in elderly mice

作　　者：王立琴[1] 杨青青 张浩[2] 周选民[3] WANG Li-qin;YANG Qing-qing;ZHANG Hao;ZHOU Xuan-min(Department of Psychosomatic Diseases,Shiyan Hospital of Traditional Chinese Medicine,Shiyan Hubei,442012,China;Department of Preventive Medicine,College of Public Health,Hubei University of Medicine,Shiyan Hubei,442000,China;Medical Imaging Center,Shiyan Taihe Hospital,Shiyan Hubei,442000,China)

机构地区：[1]十堰市中医医院心身疾病科,湖北十堰442012 [2]湖北医药学院公共卫生学院预防医学教研室,湖北十堰442000 [3]十堰市太和医院医学影像中心,湖北十堰442000

出　　处：《职业与健康》2021年第15期2042-2046,共5页Occupation and Health

基　　金：2019年十堰市科学技术研究与开发立项项目(19Y13)。

摘　　要：目的研究L-苹果酸(L malic acid,LMA)对老年小鼠铝暴露所致学习记忆损害的影响及机制。方法选取雄性16月龄昆明小鼠90只,按随机数字表法将其随机分为6组,空白组、铝染毒组、维生素C组、LMA 0.05 g/kg组、LMA 0.15 g/kg组和LMA 0.45 g/kg组,各15只;对后5组小鼠采用大脑侧脑室注入AlCl3法复制铝染毒模型,染毒结束后对LMA 0.05、0.15、0.45 g/kg组小鼠分别按0.05、0.15和0.45 g/kg LMA灌胃,1次/天,连续90天,用水迷宫测试各组潜伏期(incubation period,IP)、进入原平台象限的次数(enter number,EN)及在该象限探索的时间(enter time,ET),光度法检测海马组织超氧化物歧化酶(superoxide dismutase,SOD)活性、丙二醛(malondialdehyde,MDA)含量,Western blot法检测还原型烟酰胺腺嘌呤二核苷酸磷酸(nicotinamide adenine dinucleotide phosphate,NADPH)蛋白表达水平,酶联免疫吸附法检测可溶性淀粉样前体蛋白α(sAPPα)、β淀粉样蛋白1~42(Aβ1~42)含量。结果与空白组IP、EN、ET比较,铝染毒组小鼠IP明显延长(16.83±1.37)s,而EN明显减少(2.86±0.39)次、ET明显缩短(15.11±1.31)s,差异均有统计学意义(P<0.05),说明铝染毒模型复制成功。与铝染毒组比较,LMA 0.15 g/kg组小鼠IP明显缩短(13.55±1.51)s,EN明显增多(4.17±0.54)次、ET明显延长(17.96±1.55)s,差异有统计学意义(P<0.05);而LMA 0.45 g/kg组IP、EN、ET变化更大,差异有统计学意义(P<0.01)。与铝染毒组SOD活性、MDA含量、NADPH水平、sAPPα、Aβ1~42含量比较,LMA 0.15 g/kg组小鼠海马组织SOD活性明显提高(161.25±13.45)U/mL,MDA含量明显降低(10.01±0.94)nmol/mL,NADPH水平明显升高(8 023±431),而sAPPα含量明显提高(2.22±0.14)ng/g、Aβ1~42含量明显降低(7.01±0.62)μg/g,差异均有统计学意义(均P<0.05);而LMA 0.45 g/kg组SOD活性、MDA含量、NADPH水平、s APPα含量、Aβ1~42含量变化更大,差异均有统计学意义(均P<0.01)。结论 LMA可以明显改善铝暴露致学习记忆损害老年小Objective To investigate the effect and its mechanism of L-malic acid(LMA) on learning and memory impairment caused by aluminum exposure in elderly mice. Methods Totally 90 male kunming mice aged 16 months were selected and randomly divided into 6 groups according to the random number table method :blank group,aluminum poisoning group,vitamin C group,LMA 0.05 g/kg group,LMA 0.15 g/kg group and LMA 0.45 g/kg group,15 mice in each group. AlCl3 was injected into the lateral cerebral ventricle of the last 5 groups of mice to replicate the model of aluminum poisoning. After the infection,mice in the LMA 0.05,0.15,and 0.45 g/kg groups were given gavage at 0.05,0.15,and 0.45 g/kg LMA,respectively,once per day for 90 consecutive days. The water maze was used to test the incubation period(IP),the number of times of times each group entered the original platform quadrant(EN),and the amount of time explored in that quadrant(ET). The activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA) in hippocampal tissues were determined by photometric method. Western blot was used to detect the expression level of reduced nicotinamide adenine dinucleotide phosphate(NADPH) protein. The contents of soluble amyloid precursor protein α(sAPPα) and β-amyloid protein1-42(Aβ1~42) were determined by enzyme linked immunosorbent assay. Results Compared with the blank group,mice in aluminum poisoning group had significantly longer IP[(16.83±1.37)seconds],significantly less EN[(2.86±0.39)times] and significantly shorter ET[(15.11 ±1.31)seconds],and the differences were statistically significant(P<0.05),indicating the aluminum poisoning model replicated successfully. Compared with the aluminum poisoning group,the IP[(13.55±1.51)seconds] of the LMA 0.15 g/kg groups were significantly shortened,EN[(4.17±0.54)times]significantly increased,and ET[(17.96±1.55)seconds] significantly prolonged,and the differences were statistically significant(P <0.05). However,the changes of IP,EN and ET in LMA 0.45 g/kg group were greater,

关 键 词：阿尔茨海默病 铝 L-苹果酸 认知功能 还原型烟酰胺腺嘌呤二核苷酸磷酸 

分 类 号：R-332[医药卫生]