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目的探讨帕金森病小鼠模型中不同剂量左旋多巴对百草枯毒性作用的影响及相关机制。方法选用不同剂量左旋多巴分别在注射百草枯一定时间的C57BL小鼠(72只)腹腔内注射,利用免疫组化、W estern印迹法等观察黑质部位百草枯沉积和多巴胺能神经元变性以及α-突触核蛋白(-αSyn)聚集,并检测纤维状α-Syn经左旋多巴孵育后其聚集的改变情况。结果在注射百草枯之前腹腔注射小剂量左旋多巴抑制百草枯诱导的黑质部位多巴胺能神经元变性,α-Syn聚集减少;大剂量左旋多巴则促进黑质部位多巴胺能神经元变性。左旋多巴可以解聚已经形成的纤维状α-Syn。结论小剂量左旋多巴竞争性抑制百草枯通过血脑屏障进入中枢神经系统,起到了神经保护作用;大剂量左旋多巴则使已经形成的纤维状α-Syn解聚,出现明显的毒性作用。
Objective To investigate the effects of different doses of levodopa on paraquat toxicity in mice with Parkinson’s disease and its related mechanisms. Methods C57BL mice (72 mice) were injected intraperitoneally with different doses of levodopa for a certain period of time after injection of paraquat. Paraquat deposition and dopaminergic neuron degeneration in substantia nigra were observed by immunohistochemistry and Western blot, respectively. α-synuclein (-αSyn) was collected and the aggregation of fibrillar α-Syn was detected after incubation with levodopa. Results Low doses of L-dopa intraperitoneally injected paraquat inhibited the paraquat-induced degeneration of dopaminergic neurons in the substantia nigra and decreased the accumulation of α-Syn. Large doses of levodopa promoted the degeneration of dopaminergic neurons in substantia nigra. Levodopa can disaggregate already formed fibrous α-Syn. Conclusion Low-dose levodopa competitive inhibition of paraquat through the blood-brain barrier into the central nervous system, has played a neuroprotective role; high-dose levodopa is already formed fibrillar α-Syn depolymerization, showing significant toxic effects.