中性氨基酸对帕金森病发生干预的实验研究

Experimental study on prevention of Parkinson disease by neutral amino acid

目的探讨中性氨基酸干预帕金森病发生的作用机制。方法分别在应用百草枯建立的帕金森病小鼠模型的前后腹腔注射中性的左旋缬氨酸(L-Val)、左旋苯丙氨酸(L-Phe)、右旋缬氨酸(D-Val)及碱性的左旋赖氨酸(L-Lys),采用免疫组化、Western 印迹法观察小鼠脑黑质部位百草枯沉积以及多巴胺能神经元变性和α-突触核蛋白(α-Syn)聚集的改变。结果在应用百草枯之前注射 L-Val、L-Phe,小鼠脑黑质部位百草枯染色明显减弱,多巴胺能神经元变性及α-Syn 聚集均明显减少;而在应用百草枯之后注射,则变化不明显。以同样方式注射 D-Val 及 L-Lys,多巴胺能神经元变性及α-Syn 聚集改变也不明显。结论 L-Val、L-Phe 等左旋中性氨基酸具有竞争性抑制百草枯进入中枢神经系统的作用,并且具有结构特异性,对帕金森病的发生可以起到预防性保护作用。

Objective To investigate the effect of neutral amino acid on preventing Parkinson disease, Methods Mice were injected with L-Valine, L Pheylalanine, D-Valine or L-Lysine before or after paraquat administration, by which prakinsonian mouse model was constructed. The paraquat immunoreactivity was observed within nigral cell bodies. Then neurodegeneration and a-synuclein aggregation were observed by immunohistochemistry and Western blot. Results Paraquat immunoreactivity was abolished by the administration of L-Valine, L-Pheylalanine before paraquat exposure. Pre-treatment with these two amino acids also protected the paraquat-induced loss of nigrostriatal dopaminergic cells and formation of thioflavine S-positive aggregates. In contrast, paraquat-induced toxicity was unaffected if animals were injected with these two amino acids after paraquat exposure or pre-treated with D-Valine or L-Lysine. Conclusions Ltype neutral amino acids such as L-Valine and L-Pheylalanine can prevent paraquat-induced neurodegeneration and a-synuclein pathology through a competitive inhibition mechanism with stereospecificity in the central nervous system （CNS）. Neutral amino acid could protect the dopaminergic neuron in substantia nigra and may prevent Parkinson disease.