CAJ | 학술논문

目的探讨对氨基水杨酸钠(PAS-Na)对亚急性染锰大鼠基底核γ-氨基丁酸(GABA)、谷氨酸(Glu)、谷氨酰胺(Gln)和片氨酸(Gly)等氨基酸类神经递质水平的影响.方法将40只SD大鼠按完全随机法分为染锰组、低剂量(L-)PAS-Na(PAS)治疗组、高剂量(H-)PAS治疗组和正常对照组,每组10只.给染锰、L-PAS和H-PAS治疗组腹腔注射MnCl2·4H2O 15 mg/kg,对照组腹腔注射等容量生理盐水,每日 1次,每周5 d,共4周.分别给L-PAS治疗组、H-PAS治疗组背部皮下注射PAS-Na 100、200mg/kg,其余组背部皮下注射等容量生理盐水,每日1次,连续3周和6周.用高效液相色谱荧光检测法测定大鼠基底核Glu、Gln、Gly及GABA含量.结果 PAS-Na治疗3周时,染锰组Gly[(0.165±0.022)μmol/g]含量比对照组[(0.271±0.074)μmol/g]低(t=4.65,P＜0.05).PAS-Na治疗6周时,染锰组Glu、Gln和Gly含量[依次为(0.942±0.121)、(0.377±0.070)、(0.142±0.048)tμmol/g]均比对照组低[依次为(1.590±0.302)、(0.563±0.040)、(0.247±0.084)μmol/g;t值分别为7.72、5.85、4.30,P值均＜0.05];L-PAS治疗组、H-PAS治疗组Glu、Gln和H-PAS组Gly含量[依次为(1.268±0.124)、(1.465±0.196)、(0.497±0.050)、(0.514±0.103)、(0.219±0.034)μmol/g]均比染锰组高(L-PAS组Glu、Gln与染锰组比较,t值分别为3.89、3.77,P值均＜0.05;H-PAS组Glu、Gln、Gly与染锰组比较,t值分别为6.78、4.70、3.42,P值均＜0.05).结论锰对大鼠基底核Glu、Gln和Gly的毒作用明显,以对Gly的毒性影响出现较早,脱离锰暴露后其毒性影响仍然继续发展.PAS-Na对锰的Glu、Gln和Gly毒性影响可能有拮抗作用.
목적 탐토대안기수양산납(PAS-Na)대아급성염맹대서기저핵γ-안기정산(GABA)、곡안산(Glu)、곡안선알(Gln)화편안산(Gly)등안기산류신경체질수평적영향.방법 장40지SD대서안완전수궤법분위염맹조、저제량(L-)PAS-Na(PAS)치료조、고제량(H-)PAS치료조화정상대조조,매조10지.급염맹、L-PAS화H-PAS치료조복강주사MnCl2·4H2O 15 mg/kg,대조조복강주사등용량생리염수,매일 1차,매주5 d,공4주.분별급L-PAS치료조、H-PAS치료조배부피하주사PAS-Na 100、200mg/kg,기여조배부피하주사등용량생리염수,매일1차,련속3주화6주.용고효액상색보형광검측법측정대서기저핵Glu、Gln、Gly급GABA함량.결과 PAS-Na치료3주시,염맹조Gly[(0.165±0.022)μmol/g]함량비대조조[(0.271±0.074)μmol/g]저(t=4.65,P＜0.05).PAS-Na치료6주시,염맹조Glu、Gln화Gly함량[의차위(0.942±0.121)、(0.377±0.070)、(0.142±0.048)tμmol/g]균비대조조저[의차위(1.590±0.302)、(0.563±0.040)、(0.247±0.084)μmol/g;t치분별위7.72、5.85、4.30,P치균＜0.05];L-PAS치료조、H-PAS치료조Glu、Gln화H-PAS조Gly함량[의차위(1.268±0.124)、(1.465±0.196)、(0.497±0.050)、(0.514±0.103)、(0.219±0.034)μmol/g]균비염맹조고(L-PAS조Glu、Gln여염맹조비교,t치분별위3.89、3.77,P치균＜0.05;H-PAS조Glu、Gln、Gly여염맹조비교,t치분별위6.78、4.70、3.42,P치균＜0.05).결론 맹대대서기저핵Glu、Gln화Gly적독작용명현,이대Gly적독성영향출현교조,탈리맹폭로후기독성영향잉연계속발전.PAS-Na대맹적Glu、Gln화Gly독성영향가능유길항작용.
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) μ mol/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 seperately ( 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.