Objective 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.Methods 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.Results 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 significantlyhigher 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).Conclusion 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.%目的 研究乳酸铝暴露对大鼠学习记忆和脑脊液内β-淀粉样蛋白(Aβ)的影响.方法 SD雄性大鼠80只随机分成溶剂对照组(蒸馏水)和低、中、高剂量铝染毒组(10、30、90 mg/kg乳酸铝),每组20只,灌胃染毒2个月.采用Morris水迷宫试验检测大鼠的学习记忆能力,免疫印迹(western-blot)法检测各组大鼠脉络丛中低密度脂蛋白受体相关蛋白-1(LRP-1)表达水平,酶联免疫吸附试验(ELISA)检测脑脊液和血浆中Aβ含量.结果 Morris水迷宫试验显示,在定位航行试验中,随训练时间的延长,各组的逃避潜伏期明显缩短且差异有统计学意义(P＜0.05);随染毒剂量的增高,逃避潜伏期延长且差异有统计学意义(P＜0.05);空间探索试验中,中、高剂量组目标区域停留时间分别为(11.52±1.56)、(10.43±5.27)s,比对照组[(15.81±3.01)s]和低剂量组[(13.91±2.17)s]明显缩短,差异有统计学意义(P＜0.05);穿越平台位置次数中、高剂量组分别为(2.64±1.39)、(1.50±0.76)次,明显少于对照组[(4.29±0.914)次]和低剂量组[(3.56±1.38)次],差异有统计学意义(P＜0.05).ELISA法结果显示,与对照组[(203.46±74.36)pg/ml]比较,中、高剂量组大鼠脑脊液中的Aβ1-42含量[(320.35±84.82)、(327.68±67.51)pg/ml]明显增多,差异均有统计学意义(P＜0.05);各组血浆中Aβ1-42含量差异无统计学意义(P＞0.05).各组大鼠脑脊液和血浆中的Aβ1-40含量差异亦无统计学意义(P＞0.05).Western-blot法显示,高剂量组LRP-1蛋白相对表达量(0.57±0.21)明显低于对照组(1.00±0.00)、低剂量组(0.79±0.15)和中剂量组(0.95±0.24),差异均有统计学意义(P＜0.05).结论 亚慢性铝暴露可使大鼠学习记忆能力下降,脑脊液中的Aβ蓄积可能与脉络丛中LRP-1蛋白表达下降有关,提示铝可能通过降低LPR-1蛋白表达影响Aβ转运致Aβ蓄积进而可能影响大鼠学习记忆能力.
展开▼
