地卓西平和牛磺酸对染锰大鼠纹状体Glu-Gln环路的影响

Effect of dizocilpine maleate and taurine on the circuitry of glutamate and glutamine in rat striatum exposed by manganese

目的观察MK-801和牛磺酸对锰引起的纹状体谷氨酰胺合成酶（GS）和谷氨酰胺酶（PAG）的活性变化和纹状体谷氨酸能神经元含量的影响。方法大鼠按体重随机分成4组,每组10只,第1组为对照组,皮下注射0.9%的氯化钠;第2组为单纯染锰组,皮下注射0.9%的氯化钠;第3、4组为预处理干预组,分别皮下注射0.3μmol/kg的MK-801和1mmol/kg的牛磺酸。皮下注射2h后,第1组腹腔注射0.9%的氯化钠,第2-4组腹腔注射200μmol/kg的氯化锰,染锰25天,MK-801和牛磺酸隔日注射一次,共预处理13次。最后一次染毒后24h,每组取4只,将大鼠用乙醚麻醉,经左心室灌流固定后采集脑组织,用SABC免疫组织化学法测定纹状体谷氨酸能神经元含量。将每组另外6只大鼠直接处死,切取脑纹状体,测定GS和PAG的活性。结果单纯染锰组与对照组比较,纹状体Aa（%）和IOD明显升高,P〈0.01;纹状体GS活性降低,PAG的活性升高;MK-801预处理干预组与单纯染锰组比较,纹状体Aa（%）和IOD明显降低,GS活性明显升高,PAG活性降低;牛磺酸预处理干预组纹状体Aa（%）和IOD降低,GS活性明显升高。结论MK-801和牛磺酸对锰致大鼠Glu-Gln环路紊乱均有不同程度的拮抗作用。

Objective To observe the effect of MK-801 and taurine on the activities of GS and PAG and the glutamatic neuron content in the rat striatum exposed by manganese. Methods 40 Wistar rats were random divided into four groups. The first group was the control group which was subcutaneously injected at the content of 0.9% NaCl. The second group was MnCl2 group which was subcutaneously injected at the content of 0.9% NaCl. The third and fourth groups were pretreatment groups which were subcutaneously injected of 0.3μmol/kg MK-801 and lmmol/kg taurine. After 2h, the first group was peritoneally injected at the content of 0.9 % NaCI, the 2nd - 4th group were peritoneally injected at the dose of 200μmol/kg MnCl2 . All administration was given at the dose of 5ml/kg for 25d, the pretreatment groups were given for every other day. At the 24h after the administration of MnCl2 , the 4 rats brain tissue in every groups were removed after the rats were perfused from the left ventricles to with 4 % ploymerisatum. The glutamatic neuron content were determined by immunohistochemical method （SABC）. The activities of GS and PAG in the residual rat striatum were determined. Results In comparison with control group, the percentage of positive area and integral optical densities of glutamate immunocreative cell increased significantly in MnCI2 group （ P 〈 0.01 ）, the activity of GS decreased significantly in MnCl2 group, the activity of PAG increased significantly in MnCl2 group. In comparison with MnCl2 group, the percentage of positive area and integral optical density of glutamate immunocreative cell decreased significantly in MK-801 and taurine pretreatment group, the activity of GS increased significantly in MK-801 and taurine pretreatment group , the activity of PAG decreased significantly in MK-801 pretreatment group . Conclusion MK-801 and taurine have a certain protective effect on ＂the circuitry of glutamate and glutamine＂ disrupted with Mn.