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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 mechanism of neutral amino acids in the pathogenesis of Parkinson’s disease. Methods The effects of L-Val, L-Phe and D-Val were measured by intraperitoneal injection of paraquat in mice model of Parkinson’s disease. Val and alkaline L-lysine. Immunohistochemistry and Western blotting were used to observe the deposition of paraquat in mouse substantia nigra and the degeneration of dopaminergic neurons and the expression of α-synuclein (α- Syn) aggregation changes. Results Before paraquat injection, L-Val and L-Phe decreased paraquat staining in mouse brain substantia nigra and markedly decreased the degeneration of dopaminergic neurons and accumulation of α-Syn. However, after paraquat injection, Change is not obvious. In the same way, D-Val and L-Lys were injected, and the changes of dopaminergic neuron degeneration and α-Syn aggregation were not obvious either. Conclusion The L-Val neutral amino acids such as L-Val and L-Phe can competitively inhibit the paraquat entering the central nervous system and are structurally specific, which may play a preventive and protective role in the pathogenesis of Parkinson’s disease.