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对氨基水杨酸钠对锰暴露大鼠基底神经节氨基酸神经递质浓度的影响

[Effect of sodium para-aminosalicylic on concentrations of amino acid neurotransmitters in basal ganglia of manganese-exposed rats].

作者信息

Ou Chao-yan, Huang Ming-li, Jiang Yue-ming, Luo Hai-lan, Deng Xiang-fa, Wang Chan, Wang Fang, Huang Xiao-wei

机构信息

School of Public Health, Guangxi Medical University, Nanning 530021, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2011 May;45(5):422-5.

Abstract

OBJECTIVE

To probe the effect of sodium para-aminosalicylate (PAS-Na) on concentration of amino acid neurotransmitters including glutamate (Glu), glutamine (Gln), glycine (Gly) and gamma-aminobutyric acid (GABA) in basal ganglia of subacute manganese (Mn)-exposed rats.

METHODS

Forty Sprague-Dawley male rats were randomly divided into the control, Mn-exposed, low dose PAS-Na (L-PAS) and high dose PAS-Na (H-PAS) groups. Rats in experiment groups received daily intraperitoneally injections of manganese chloride (MnCl₂ · 4H₂O, 15 mg/kg), while rats in control group received daily intraperitoneally injections of normal saline (NS), all at 5 days/week for 4 weeks. Then the rats in PAS groups followed by a daily subcutaneously dose of PAS-Na (100 and 200 mg/kg as the L-PAS and H-PAS groups, respectively) for another 3 and 6 weeks; while the rats in Mn-exposed and control group received NS. The concentrations of Glu, Gln, Gly and GABA in basal ganglia of rat was detected by the high performance liquid chromatography fluorescence detection technique.

RESULTS

After treating with PAS-Na for 3 weeks, the concentration of Gly in the Mn-exposed rats decreased to (0.165 ± 0.022) µmol/L (control = (0.271 ± 0.074) µmol/L, Mn vs control, t = 4.65, P < 0.05). After the further 6-week therapy with PAS-Na, the concentrations of Glu, Gln, Gly in the Mn-exposed rats were lower than those of the control rats ((0.942 ± 0.121), (0.377 ± 0.070), (0.142 ± 0.048), (1.590 ± 0.302), (0.563 ± 0.040), (0.247 ± 0.084) µmol/L; t = 7.72, 5.85, 4.30, P < 0.05); and also lower than in L-PAS and H-PAS groups, whose concentrations were separately (1.268 ± 0.124), (1.465 ± 0.196), (0.497 ± 0.050), (0.514 ± 0.103), (0.219 ± 0.034) µmol/L (L-PAS Glu and Gln vs Mn, t = 3.87, 3.77, P < 0.05; H-PAS Glu, Gln and Gly vs Mn, t = 6.78, 4.70, 3.42, P < 0.05).

CONCLUSION

The toxic effect of manganese on Glu, Gln and Gly in basal ganglia of Mn-exposed rats is obvious, especially appears earlier on Gly. The toxic effect still continues to develop when relieved from the exposure. PAS-Na may play an antagonism role in toxic effect of manganese on concentration of Glu, Gln and Gly in basal ganglia of Mn-exposed rats.

摘要

目的

探讨对氨基水杨酸钠(PAS-Na)对亚急性锰(Mn)暴露大鼠基底神经节中谷氨酸(Glu)、谷氨酰胺(Gln)、甘氨酸(Gly)和γ-氨基丁酸(GABA)等氨基酸神经递质浓度的影响。

方法

将40只雄性Sprague-Dawley大鼠随机分为对照组、锰暴露组、低剂量PAS-Na(L-PAS)组和高剂量PAS-Na(H-PAS)组。实验组大鼠每日腹腔注射氯化锰(MnCl₂·4H₂O,15mg/kg),对照组大鼠每日腹腔注射生理盐水(NS),均每周5天,共4周。然后PAS组大鼠分别每日皮下注射PAS-Na(L-PAS组和H-PAS组分别为100和200mg/kg),持续3周和6周;而锰暴露组和对照组大鼠注射NS。采用高效液相色谱荧光检测技术检测大鼠基底神经节中Glu、Gln、Gly和GABA的浓度。

结果

PAS-Na治疗3周后,锰暴露大鼠的Gly浓度降至(0.165±0.022)μmol/L(对照组为(0.271±0.074)μmol/L;锰暴露组与对照组比较,t = 4.65,P < 0.05)。PAS-Na进一步治疗6周后,锰暴露大鼠的Glu、Gln、Gly浓度低于对照组大鼠(分别为(0.942±0.121)、(0.377±0.070)、(0.142±0.048)、(1.590±0.302)、(0.563±0.040)、(0.247±0.084)μmol/L;t = 7.72、t = 5.85、t = 4.30,P < 0.05);也低于L-PAS组和H-PAS组,L-PAS组和H-PAS组的浓度分别为(1.268±0.124)、((1.465±0.196)、(0.497±0.050)、(0.514±0.103)、(0.219±0.034)μmol/L(L-PAS组的Glu和Gln与锰暴露组比较,t = 3.)87、t = 3.77,P < 0.05;H-PAS组的Glu、Gln和Gly与锰暴露组比较,t = 6.78、t = 4.70、t = 3.42,P < 0.05)。

结论

锰对锰暴露大鼠基底神经节中Glu、Gln和Gly的毒性作用明显,尤其是对Gly的毒性作用出现较早。脱离暴露后,毒性作用仍持续发展。PAS-Na可能对锰暴露大鼠基底神经节中Glu、Gln和Gly浓度的毒性作用具有拮抗作用。

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