氯丙嗪和尼莫地平对锰致大鼠神经毒性的影响

目的观察氯丙嗪（CPZ）和尼莫地平（NIMO）对锰致大鼠脑纹状体谷氨酰胺合成酶（GS）、磷酸活化的谷氨酰胺酶（PAG）、脑皮质Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶活力和脑丙二醛（MDA）含量的影响。方法32只大鼠按体重随机分成4组，第1组大鼠为对照组，腹腔注射0.9％的氯化钠；第2组为染锰组，腹腔注射0.9％的氯化钠；第3和4组为预处理干预组，分别腹腔注射14.1μmol·kg^-1CPZ和2.4mmol·kg^-1NIMO。腹腔注射后2h，第1组大鼠皮下注射0.9％的氯化钠，第2-4组皮下注射200μmol·kg^-1的氯化锰。给大鼠连续注射4周，每周5d。最后一次染毒后24h，将大鼠处死，断头取出脑纹状体和大脑皮质，测定脑纹状体GS、PAG和脑皮质Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶活力、MDA含量。结果与对照组比较，单纯染锰组大鼠脑纹状体GS活力明显降低，PAG活力明显升高；脑皮质Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶的活力明显降低，MDA含量增加。与单纯染锰组比较，CPZ处理组大鼠脑纹状体GS活力升高；脑皮质Na^＋-K^＋-ATP酶和Ca^2＋-ATP酶活力上升，MDA含量下降；NIMO预处理组大鼠脑纹状体GS的活力升高，PAG的活力降低。脑皮质Na^＋-K^＋-ATP酶和Ca^2＋-ATP酶活力上升。结论锰可致大鼠脑Gs、Na^＋-K^＋-ATPase酶和Ca^2＋-ATP酶活力降低，PAG活力升高，MDA含量增加。CPZ和NIMO对锰所致神经毒性有一定的拮抗作用。

The effects of chlorpromazine and nimodipine on neurotoxicity induced by manganese in rats

Aim To investigate the effects of manganese on the activities of glutamine synthetase （GS） , phosphate activated glutaminase （PAG） , Na^＋-K^＋-ATPase, Ca^2＋-ATPase and the content of malondialdehyde （MDA） and to observe the effect of chlorpromazine （CPZ） and nimodipine （NIMO） on manganese-induced neurotoxicity in rats. Methods The 32 Wistar rats were divided into four groups by weight at random. The first group is the control group and the second group is the manganese exposed group. The first and second groups were intraperitoneally （ip） injected with 0.9% sodium chloride. The third and fourth groups were intervention groups and were ip injected with 14.1μmol·kg^-1 of CPZ and 2.4 mmol·kg^-1 of NIMO, respectively. Two hours after ip injections, the animals in the control group were subcutaneously （sc） injected with 0.9% sodium chloride, the second to forth groups were sc injected with 200μmol·kg^-1 MnC12. The animals were injected for 4 weeks, 5 days a week. At the 24h after the last injection, the activities of PAG, GS in the corpus striatum, the activities of Na^＋-K^＋-ATPase, Ca^2＋-ATPase and the content of MDA in cerebral cortex were determined. Results Compared with the control group, the activity of GS was significantly decreased and PAG increased in the corpus striatum,the activities of Na^＋-K^＋-ATPase and Ca2^＋-ATPase decreased, the content of MDA increased in cerebral cortex in the group given 200μmol·kg^-1 MnC12. In the groups pretreated with CPZ and NIMO, the activities of GS, Na^＋-K^＋-ATPase and Ca^2＋-ATPase were significantly increased compared with 200μmol·kg^-1 MnC12 group. The activity of GS was significantly decreased in the group pretreated with CPZ and the content of MDA decreased in NIMO group. Conclusion Manganese resulted in the reduction of GS, Na^＋-K^＋-ATPase, Ca^2＋-ATPase activities ,the increase of PAG activity and MDA content. Pretreatment with CPZ and NIMO can antagonize neurotoxicity induced by manganese to a certain ex