目的 研究铝亚慢性染毒对大鼠学习记忆能力及组蛋白H3第4位赖氨酸(H3K4)甲基转移酶(MLL)的影响。方法 无特定病原体级健康雄性SD大鼠40只按体质量随机分为对照组和低、中、高剂量组,每组10只。采用饮水染毒法,对照组给予灭菌自来水,低、中、高剂量组分别每日给予剂量为2、12、72mg/kg体质量的铝染毒,连续染毒90d。染毒结束后,采用Morris水迷宫实验测定大鼠学习记忆能力,采用组蛋白甲基转移酶活性/抑制性试剂盒测定海马组织中MLL活力,采用实时荧光定量聚合酶链反应法测定海马组织中MLL相对表达量。结果 Morris水迷宫实验结果显示:定位航行实验中,大鼠逃避潜伏期在染铝处理与训练时间的交互作用上无统计学意义(P〉0.05),大鼠逃避潜伏期在染铝处理的主效应上无统计学意义(P〉0.05),但在训练时间的主效应上有统计学意义(P〈0.05);空间探索实验中,中和高剂量组大鼠穿越平台位置次数均少于对照组(P〈0.05),高剂量组目标象限停留时间短于对照组(P〈0.05)。中和高剂量组大鼠海马组织中MLL活力均低于对照组(P〈0.01),高剂量组MLL活力分别低于低和中剂量组(P〈0.05)。各组大鼠海马组织中MLL相对表达量比较,差异无统计学意义(P〉0.05)。结论 亚慢性铝暴露可导致大鼠学习记忆能力下降及海马组织中MLL活力降低,提示铝可能通过降低MLL进而影响学习记忆能力。
Objective To investigate the effect of subchronic aluminum( Al) exposure to learning and memory ability and histone H3 lysine 4( H3K4) methyltransferase( MLL) in rats. Methods Forty specific pathogen free healthy male SD rats were randomly divided into 4 groups by body weight with 10 rats in each group. They were a control group( 0 mg / kg Al3 +),and low-( 2 mg/kg Al3 +),medium-( 12 mg/kg Al3 +) and high-dose( 72 mg/kg Al3 +) exposure groups. Each group was treated with indicated doses of Al3 +in drinking water for continuous 90 days. After the exposure,Morris water maze test was performed to assess the learning and memory abilities of the rats. The MLL activity of hippocampus was detected using histone methyltransferase activity / inhibition assay kit and relative expression of MLL of hippocampus was measured by real-time fluorescent quantitative polymerase chain reaction. Results In place navigation trial of Morris water maze test,the interaction effect of Al treatment and training time showed no significant difference in the escape latency( P〉0. 05),the escape latency of rats had no significant difference in main effect with Al treatment( P〉0. 05),but the main effect of training time showed statistical significant difference( P〈0. 05). Times of passing through the original platform in the medium- and high-dose exposure groups were less than those of the control group in spatial probe test( P〈0. 05). The target quadrant residence time was shorter in the high-dose exposure group compared with that of the control group( P〈0. 05). The MLL enzyme activity was significantly decreased in the medium- and high-dose exposure groups compared with that of control group( P〈0. 01),moreover,it was significantly lower in high-dose exposure group than in the low- and medium-dose exposure groups( P〉0. 05). However,the relative expression of MLL in all groups showed no significant difference( P〈0. 05). Conclusion Sbuchronic Al exposure resulted