铝螯合剂对铝染毒大鼠学习记忆及兴奋性氨基酸类神经递质的影响

Effect of Aluminum Chelating Agent on Learning and Memory and Excitatory Amino Acids Neurotransmitters in Rats Exposed to Aluminum

目的探讨铝螯合剂1,2-二甲基-3-羟基-4-吡啶酮(DFP)对铝染毒大鼠学习和记忆能力以及脑组织中天门冬氨酸(Asp)、谷氨酸(G1u)两种兴奋性氨基酸类神经递质含量的影响。方法将SPF级健康雄性Wistar大鼠35只按体重随机分为5个组,分别为阴性对照组(给予1 ml/d生理盐水,连续10周),铝染毒组[前8周给予AlCl_3 354.7 mg/(kg·d),后2周给予生理盐水1 ml/d],铝+DFP低、中、高剂量组[前8周给予AlCl_3 354.7 mg/(kg·d),后2周分别给予DFP 13.82、27.44、54.88 mg/(kg·d)],每组7只,均以灌胃方式染毒。采用Y型迷宫实验观察大鼠学习记忆能力的改变,采用高效液相色谱法测定各组大鼠脑组织中Asp、Glu的含量。结果各组大鼠体重间比较,差异无统计学意义(P>0.05)。Y型迷宫实验结果显示,铝+DFP高剂量组潜伏期短于铝染毒组,差异均有统计学意义(P<0.05);且各铝+DFP剂量组潜伏期与阴性对照组比较,差异均无统计学意义(P>0.05)。铝染毒组大鼠错误次数多于阴性对照组,各铝+DFP剂量组错误次数均少于铝染毒组,差异均有统计学意义(P<0.05);各铝+DFP剂量组错误次数与阴性对照组比较,差异均无统计学意义(p>0.05)。铝+DFP低、中、高剂量组天门冬氨酸和谷氨酸含量均高于铝染毒组,低于阴性对照组,差异均有统计学意义(P<0.01)。结论DFP能够升高染铝大鼠脑组织中兴奋性氨基酸类神经递质含量,有效地改善染铝大鼠学习记忆能力,对中枢神经系统有明显的保护作用。

Objective To inquire the effects of 1,2-dimethyl-3-hydroxypyrid-4-pyridine （DFP） on learning and memory and two excitatory amino acid neurotransmitters alteration. Methods Thirty-five male Wistar rats of SPF grade, adult and healthy, were randomly divided into five groups based on their body weight. The negative control group were administered with NS （1 ml/d） for 10 weeks,the aluminum treated group were administered with 354.7 mg/（kg· d） aluminum chloride for 8 weeks, then treated with NS （1 ml/d） for another 2 weeks. The low, mid, high dose groups （AI＋DEP） were administered with 354.7 mg/（kg·d） aluminum chloride for 8 weeks, then treated with different doses of 13.82, 27.44, 54.88 mg/（kg· d） DFP for another 2 weeks. The treatment was conducted by garage. Maze test was used to test the learning and memory alteration. HPLC-UV method was used to determine amino acid neurotransmitters in the brain. Results The body weight of all groups showed no significantly difference （P〉0.05）. Maze test found that the latent period of high dose group （Al＋DFP） were significantly lower than the aluminum treated group （P〈 0.01）, compared with the negative control group, the latent period of the three different dose groups （Al ＋DFP） showed no significantly difference （P〉0.05） and the error time of the aluminum treated group were higher than the negative control group （P〈 0.05）, the error time of the three different dose groups （Al＋DFP） was significantly lower than the aluminum treated group （P〈0.01）. The content of Asp and Glu of the three different dose groups （Al＋DFP） were significantly higher than the aluminum treated group （P〈0.01） and lower than the negative control group （P〈0.01）. Conclusion DFP can effectively increase the excitatory amino acids neurotransmitters in rats exposed to aluminum and improve the learning and memory ability and protect the central nervous system.