氯化锰致大鼠神经毒性机制的研究

Study on neurotoxicity mechanism induced by manganese chloride in rats

为研究不同剂量的氯化锰对大鼠脑纹状体谷氨酰胺合成酶(GS)、磷酸激活的谷氨酰胺酶(PAG)和大脑皮质Na+-K+-ATPase和Ca2+-ATPase活力的影响,将32只SD大鼠,按体重随机分成4组。第1组为对照组,皮下注射生理盐水,第2～4组为不同剂量染锰组,分别皮下注射50、100和200μmol/kg的氯化锰溶液,每周注射5次,连续染毒4周。观察大鼠体重变化和一般表现。最后一次注射后24h处死大鼠,切取纹状体,测定GS和PAG的活力;切取大脑皮质,测定Ca2+-ATPase和Na+-K+-ATPase的活力。结果显示,随着染锰剂量的增加,脑纹状体GS活力降低,PAG活力升高,大脑皮质Ca2+-ATPase和Na+-K+-ATPase活力降低。与对照组比较,在50、100和200μmol/kg染锰组GS和Na+-K+-ATPase活力逐渐下降,差异有统计学意义;在100和200μmol/kg染锰组PAG的活力逐渐升高,Ca2+-ATPase活力逐渐下降,且差异有统计学意义。说明不同剂量氯化锰可引起大鼠脑纹状体GS活力降低,PAG活力升高;大脑皮质Na+-K+-ATPase和Ca2+-ATPase活力降低,由此可引起谷氨酸代谢失衡,产生神经毒性。

To study the effects of different doses of manganese chloride on activities of glutamine synthetase （GS） and phosphate activated glutaminase （PAG） in striatum and the activities of Na^＋ -K ^＋ -ATPase and Ca^2＋ -ATPase in cerebral cortex of rats. 32 SD rats were divided into four groups by weight at random. The rats in first group were subcutaneously injected with 0. 9% sodium chloride, the rats in other three groups were injected with 50, 100 and 200 （μmol/kg respectively for 4 weeks, 5 days a week. At the 24h after the last injection, the activities of GS, PAG in striatum and the activaies of Na^＋ -K ^＋ -ATPase and Ca^2＋ -ATPase in cerebral cortex were determined. The results showed that with the increase of manganese dosage, PAG activity increased, especially in 100 and 200 μmol/kg MnCl2 groups ; while the activities of GS and Na^＋ -K ^＋ -ATPase and Ca^2＋-ATPase were all decreased. It indicated that manganese could induce decrease of GS activity, increase of PAG activity in striatum, and increase of Na ^＋ -K^＋ -ATPase and Ca^2＋-ATPase activities in cerebral cortex , thereby leading to the imbalance of glutamate metabolism and producing neurotoxicity.