对氨基水杨酸钠对染锰大鼠基底核GABAAR及GAT-1表达的影响
Effect of PAS-Na on GABAAR and GAT-1 Protein and mRNA Levels in Basal Ganglia of ManganeseExposed Rats
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摘要:
目的 探讨对氨基水杨酸钠(PAS-Na)对短期或亚慢性染锰大鼠基底核 γ-氨基丁酸(gamma-aminobutryic acid, GABA)A受体(GABAAreceptor, GABAAR)及 GABA转运载体 -1(GABA transporter-1, GAT-1)表达的影响。 方法 将短期实验大鼠分为染锰组、PAS低(L-)、高(H-)剂量治疗组和对照组, 观察期为 7、10周; 将亚慢性实验大鼠分为对照组、染锰组、PAS预防组和 PAS低(L-)、中(M-)、高(H-)剂量治疗组, 观察期为 4、8、12、18周。用实时荧光定量聚合酶链反应(RT-PCR)、免疫印迹法(Western blot)检测大鼠脑基底核 GABAAR及 GAT-1表达。 结果 短期实验中, 观察期 7周, 染锰组 GABAAR蛋白表达较对照组高(P < 0.05); 观察期 10周, 染锰组 GABAAR和 GAT-1 mRNA表达较对照组低,L-PAS、H-PAS治疗组基底核 GAT-1 mRNA表达较染锰组高(P < 0.05)。亚慢性实验中, 观察期 4周, 染锰组 GABAAR mRNA表达较对照组高(P < 0.05); 观察期 8周, 染锰组 GABAAR mRNA表达较对照组低, 预防组 GABAAR mRNA 表达较染锰组高(P < 0.05)。观察期 12周, 染锰组 GABAAR 蛋白表达较对照组高, 预防组 GABAAR 蛋白表达较染锰组低(P < 0.05)。观察期 18周, 染锰组 GABAAR mRNA表达较对照组低, GAT-1 mRNA表达较对照组高, H-PAS治疗组 GAT-1 mRNA表达较染锰组低(P < 0.05)。 结论 短期或亚慢性锰暴露对大鼠基底核 GABAAR和 GAT-1 mRNA表达都有明显的毒性影响,PAS-Na对亚慢性锰暴露致 GABAAR mRNA或蛋白表达改变有预防性干预作用, 对锰致大鼠基底核 GAT-1 mRNA表达改变有治疗性干预作用。 Abstract:Objective To explore the effect of sodium para-aminosalicylate (PAS-Na) on the expression of gammaaminobutryic acid type A receptor (GABAAR) and gamma-aminobutryic acid transporter (GAT-1) in short-term or subchronic manganese (Mn)-exposed rats. Methods In the short-term experiment, rats were divided into control, Mn-exposed, lowdose PAS-Na (L-PAS) and high-dose PAS-Na (H-PAS) groups, each subgroup of 10 rats were necropsied at the end of week 7 and 10. In the subchronic experiment, rats were divided into control, Mn-exposed, PAS-Na prevention (P-PAS), and L-PAS, M-PAS (middle-dose PAS-Na) and H-PAS groups, and were observed at week 4, 8, 12 and 18. The mRNA and protein expression of GABAAR and GAT-1 in rat basal ganglia were examined by real-time fluorescence polymerase chain reaction (RT-PCR) and Western blot (WB). Results In the short-term experiment, on observation week 7, GABAAR protein expression was significantly increased in Mn-exposed group (P < 0.05); on observation week 10, GABAAR and GAT-1 mRNA expression were significantly decreased in Mn-exposed rats (P < 0.05), and L-PAS and H-PAS treatment restored their GAT-1 mRNA expression (P < 0.05). In the subchronic experiment, on obervation week 4, GABAAR mRNA expression was greatly increased in Mn-exposed rats (P < 0.05); on observation week 8, GABAAR mRNA expression was greatly decreased in Mn-exposed rats vs controls (P < 0.05) and increased in P-PAS group vs Mnexposed rats (P < 0.05); however, on obervation week 12, GABAAR protein expression was greatly increased in Mn-exposed rats vs controls (P < 0.05) and decreased in P-PAS vs Mn-exposed rats (P < 0.05); on observation week 18, GABAAR mRNA expression was greatly decreased in Mn-exposed rats vs controls (P < 0.05), and GAT-1 mRNA expression was greatly increased in Mn-exposed rats vs controls (P < 0.05) and decreased in H-PAS vs Mn-exposed rats (P < 0.05). Conclusion Short-term and subchronic exposure of manganese exhibited obvious toxic effects in the expression of mRNA GABAAR and GAT-1 in basal ganglions of rats. PAS-Na played a preventive intervention role in the GABAAR mRNA or protein expression of subchronic Mn-exposed rats and a therapeutic intervention role in the GAT-1 mRNA expression.
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