Wu X H, Pang Y X, Qiu H Y, Chen J P, Zhang Q L, Niu Q
Department of Occupational and Environmental Health, Shanxi Medical University, Taiyuan 030001, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2016 Feb 20;34(2):90-4. doi: 10.3760/cma.j.issn.1001-9391.2016.02.003.
To investigate the effects of aluminum lactate exposure on learning and memory and the transportation of amyloid-beta peptides(Aβ) in cerebrospinal fluid in rats.
A total of 80 male Sprague-Dawley rats were randomly divided into solvent control(distilled water) group and low-, medium-, and high-dose aluminum poisoning groups(10, 30, and 90 mg/kg aluminum lactate), with 20 rats in each group, and the poisoning procedure was performed by gavage for 2 months. The Morris water maze test was used to test the rats' learning and memory, Western blot was used to measure the expression level of low-density lipoprotein receptor protein-1(LRP-1) in rats' choroid plexus, and enzyme-linked immunosorbent assay(ELISA) was used to measure the content of Aβ in the cerebrospinal fluid and plasma.
The Morris water maze test showed that in the place navigation test, with the increasing training time, the escape latency was significantly shortened in each group and showed significant differences between any two groups(P<0.05). In the spatial probe test, the time spent in target quadrant in the medium-and high-dose groups was 11.52±1.56 s and 10.43±5.27 s, respectively, which was significantly shorter than that in the control group and the low-dose group(15.81±3.01 s and 13.91±2.17 s)(P<0.05). The numbers of platform crossings in the medium-and high-dose groups were 2.64±1.39 and 1.50±0.76, respectively, which were significantly lower than those in the control group and the low-dose group(4.29±0.914 and 3.56±1.38)(P<0.05). The results of ELISA showed that the medium-and high-dose groups had significant increases in the content of Aβ1-42 in cerebrospinal fluid(320.35±84.82 pg/ml and 327.68±67.51 pg/ml), which was significantly higher than that in the control group(203.46±74.36 pg/ml) (P<0.05). The content of Aβ1-42 in plasma showed no significant difference between any two groups(P>0.05), and that of Aβ1-40 in cerebrospinal fluid and plasma also showed no significant difference between any two groups(P>0.05). The results of Western blot showed that the high-dose group had significantly lower protein expression of LRP-1 than the control group and the low-and medium-dose groups(0.57±0.21 vs 1.00±0.00/0.79±0.15/0.95±0.24, P<0.05).
Subchronic aluminum exposure may reduce learning and memory in rats, and the accumulation of Aβ in cerebrospinal fluid may be related to the reduced protein expression of LRP-1 in the choroid plexus, suggesting that aluminum affects learning and memory in rats through reducing the protein expression of LRP-1, influencing the transportation of Aβ, and leading to the accumulation of Aβ.
探讨乳酸铝暴露对大鼠学习记忆及脑脊液中β淀粉样肽（Aβ）转运的影响。
将80只雄性Sprague-Dawley大鼠随机分为溶剂对照组（蒸馏水）和低、中、高剂量铝中毒组（乳酸铝剂量分别为10、30和90mg/kg），每组20只，经口灌胃染毒2个月。采用Morris水迷宫试验检测大鼠学习记忆能力，Western blot法检测大鼠脉络丛中低密度脂蛋白受体相关蛋白-1（LRP-1）的表达水平，酶联免疫吸附测定（ELISA）法检测脑脊液和血浆中Aβ的含量。
Morris水迷宫试验结果显示，在定位航行试验中，随着训练时间延长，各组逃避潜伏期均显著缩短，且任意两组间差异均有统计学意义（P<0.05）。在空间探索试验中，中、高剂量组在目标象限停留时间分别为11.52±1.56秒和10.43±5.27秒，显著短于对照组和低剂量组（15.81±3.01秒和13.91±2.17秒）（P<0.05）。中、高剂量组穿越平台次数分别为2.64±1.39次和1.50±0.76次，显著低于对照组和低剂量组（4.29±0.914次和3.56±1.38次）（P<0.05）。ELISA检测结果显示，中、高剂量组脑脊液中Aβ1-42含量显著升高（320.35±84.82pg/ml和327.68±67.51pg/ml），显著高于对照组（203.46±74.36pg/ml）（P<0.05）。血浆中Aβ1-42含量在任意两组间差异均无统计学意义（P>0.05），脑脊液和血浆中Aβ1-40含量在任意两组间差异也均无统计学意义（P>0.05）。Western blot检测结果显示，高剂量组LRP-1蛋白表达显著低于对照组及低、中剂量组（0.57±0.21 vs 1.00±0.00/0.79±0.15/0.95±0.24，P<0.05）。
亚慢性铝暴露可能导致大鼠学习记忆能力下降，脑脊液中Aβ蓄积可能与脉络丛中LRP-1蛋白表达降低有关，提示铝可能通过降低LRP-1蛋白表达，影响Aβ转运，导致Aβ蓄积，进而影响大鼠学习记忆。
