关键词: 帕金森病, 1-甲基-4-苯基-1, 2, 3, 6-四氢吡啶, 成纤维细胞生长因子20, A型K+电流, 长时程增强, Kv4.2, 氧化应激, 丙二醛, 运动, 神经再生

Abstract:

Genome-wide studies have reported that Parkinson’s disease is associated with abnormal expression of various growth factors. In this study, male C57BL/6 mice aged 10 weeks were used to establish Parkinson’s disease models using an intraperitoneal injection of 60 mg/kg 1-meth¬yl-4-phenyl-1,2,3,6-tetrahydropyridine. 28 days later, 10 or 100 ng fibroblast growth factor 20 was injected intracerebroventricularly. The electrophysiological changes in the mouse hippocampus were recorded using a full-cell patch clamp. Expression of Kv4.2 in the substantia nigra was analyzed using a western blot assay. Serum malondialdehyde levels were analyzed by enzyme-linked immunosorbent assay. The motor coor¬dination of mice was evaluated using the rotarod test. The results showed that fibroblast growth factor 20 decreased A-type potassium current in neurons of the substantia nigra, increased long-term potentiation amplitude in the hippocampus, and downregulated Kv4.2 expression. A high dose of fibroblast growth factor 20 reduced serum malondialdehyde levels and enhanced the motor coordination of mice. These findings confirm that fibroblast growth factor 20 has a therapeutic effect on the toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and its mecha¬nism of action is associated with the inhibition of A-type K+ currents and Kv4.2 expression. All animal procedures were approved by the Animal Care and Use Committee of Qilu Hospital of Shandong University, China in 2017 (approval No. KYLL-2017-0012).

Key words: nerve regeneration, Parkinson’s disease, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, fibroblast growth factor 20, A-type potassium current, long-term potentiation, Kv4.2, oxidative stress, malondialdehyde, motor performance, neural regeneration