褪黑素对锰中毒大鼠脑谷氨酸代谢和转运的影响

Effects of melatonin on metabolism and transport of glutamate in brain of manganese poisoned rats

目的探讨氯化锰对大鼠脑谷氨酸代谢和转运的影响及褪黑素的干预作用,为锰中毒的防治提供理论依据。方法 Wistar大鼠24只,按体重随机分成3组,每组8只。第1组为对照组,腹腔注射0.9%氯化钠,第2组为单纯染锰组,腹腔注射0.9%氯化钠,第3组为褪黑素干预组,腹腔注射21.5μmol/kg褪黑素,2 h后第1组皮下注射生理盐水,第2组和第3组皮下注射200μmol/kg氯化锰。注射容量均为5 ml/kg,每日注射1次连续染毒4周;染毒结束后24 h,将大鼠用乙醚麻醉,腹主动脉取血,断头分离大脑纹状体和皮质;测定脑纹状体谷氨酸合成酶(GS)、谷氨酰胺酶(PAG)的活性,大脑皮质Na+-K+-ATP酶活性、Ca2+-ATP酶活性和丙二醛(MDA)含量。结果与对照组比较,单纯染锰组GS、Na+-K+-ATP和Ca2+-ATP酶降低14.93%、54.19%和46.55%,MDA含量和PAG酶活性分别升高1.54倍和1.43倍。与单纯染锰组比较,褪黑素干预组中GS、Na+-K+-ATP和Ca2+-ATP酶分别升高至1.13、1.62和1.35倍,MDA含量降低13.36%,PAG酶活性未见改变。结论锰能导致大鼠脑谷氨酸代谢和转运障碍,褪黑素对其有一定的拮抗作用。

Objective To study the effect of manganese on the metabolism and transport of glutamate,and the intervention effect of melatonin on them.Methods 24 Wistar rats were randomly divided into three groups according to weight.The first was the control group given intraperitoneal（ip）injection of 0.9% NaCl only;the second was manganese exposed group received ip injection of 0.9% NaCl（5 ml/kg）first;the third was melatonin intervention group which was injected ip with 21.5 μmol/kg melatonin.Two hours later,the control group was given subcutaneous（sc）injection of 0.9% NaCl（5ml/kg）again,the second and third group were given sc injection of 200 μmol/kg MnCl2 once a day,for 4 weeks.24 hours after last injection,the activities of GS（glutamate synthetase）and PAG（phosphate-activated glutaminase）in striatum and the activities of Na＋-K＋ ATPase and Ca2＋-ATPase,the content of MDA in cerebral cortex were determined.Results Compared with control group,the activities of GS,levels of Na＋-K＋-ATPase and Ca2＋-ATPase in manganese-exposed group were reduced 14.93%,54.19% and 46.55%respectively,the content of MDA and the activity of PAG were increased 1.54 and 1.43 times respectively while the activities of GS,Na＋-K＋-ATPase,and Ca2＋-ATPase in melatonin group were 1.13,1.62 and 1.35 times increased,the MDA content also showed obvious decrease compared with the manganese-exposed group.Conclusion The results suggested that manganese may cause dysfunction of glutamate in metabolism and transport,melatonin shows a definite antagonistic effect on it.