胍丁胺和尼莫地平对锰致大鼠兴奋性毒性影响

Effect of agmatine and nimodipine on excitotoxicity induced by manganese in rats

目的研究胍丁胺和尼莫地平对锰引起的大鼠脑纹状体谷氨酰胺合成酶、磷酸激活的谷氨酰胺酶和脑皮质Na+-K+-ATP酶、Ca2+-ATP酶活性变化的影响。方法32只大鼠按体重随机分成4组,第1组为对照组;第2组为单纯染锰组,第3,4组分别为胍丁胺和尼莫地平预处理干预组,连续干预并染锰4周。最后1次染毒后24h,将每组大鼠直接处死,断头取脑,在冰浴下分离脑纹状体和皮质,应用比色法测定脑纹状体中谷氨酰胺合成酶、磷酸激活的谷氨酰胺酶和脑皮质中Na+-K+-ATP酶和Ca2+-ATP酶的活性。结果在单纯染200μmol/kg的氯化锰组中,谷氨酰胺合成酶〔(50.41±5.47)U/(min.g.pro)〕、Na+-K+-ATP酶(2.13±0.15)μmol/(h.mg)、Ca2+-ATP酶(0.56±0.28)μmol/(h.mg),3种酶与对照组比较活性明显降低(P<0.01),磷酸激活的谷氨酰胺酶(72.24±9.38)μmol/(min.g.pro),与对照组比较活性明显升高(P<0.01);而21.9μmol/kg的胍丁胺和2.4 mmol/kg的尼莫地平预处理干预组与单纯染锰组比较,谷氨酰胺合成酶、Na+-K+-ATP酶、Ca2+-ATP酶活性明显升高(P<0.01),磷酸激活的谷氨酰胺酶活性明显降低(P<0.01)。结论胍丁胺和尼莫地平对锰致大鼠兴奋性毒性有一定的保护作用。

Objective To determine whether agrnatine and nimodipine can prevent the toxic effects of manganese on glutamine synthetase, phosphate activated glutaminase, Na^＋ - K^＋ - ATPase and Ca^2＋ - ATPase in rat striatum. Methods 32 Wistar rats were divided into four groups by weight at randomization. The first group was the control group, the second group was given MnCl2 only. The third and fourth groups were given agmatine and nimodipine respectively. The administration lasted 4 weeks. 24 hours after the last injection, the activities of glutamine synthetase and phosphate activated glutaminase in striatum, the activities of Na^＋ - K^＋ - ATPase and Ca^2＋ - ATPase in pallium were determined. Results Compared with the control group, the activities of glutamine synthetase [（50.41 ± 5.47）U/（min·g·pro）], Na^＋ - K^＋ - ATPase [（2.13 ± 0.15）μmol/（h·mg）]and Ca^2＋ - ATPase [（0.56 ± 0.28）μmol/（h·mg）] in the second group decreased significantly（P〈0.01 ）. The activity of phosphate activated glutaminase [ （ 72.24 ± 9.38） μmol/min· g· pro） ] increased significantly（ P 〈 0.01 ）. Compared with the second group, the activities of glutamine synthetase, Na^＋ - K^＋ - ATPase and Ca^2＋ - ATPase in the third and fourth groups increased significantly（ P 〈 0.01 ）. And the activity of phosphate activated glutaminase decreased significantly（ P 〈 0.01 ）. Conclusion Agmatine and nimodipine have certain protective effects on the excitotoxicity induced by manganese in Wistar rats.