Parkinson's disease (PD) is a neurodegenerative disease which results in damage in neuronal cells. Insulin‐like growth factor (IGF)‐1 was previously reported to play a role of neuroprotection in some diseases. Nitric oxide (NO) can also regulate neuronal cells. However, the mechanisms underlying IGF‐1 and NO in PD still need to be elucidated. In present study, we explored the interaction between IGF‐1 and inducible Nitric‐Oxide Synthase (iNOS) in PD progression. We firstly constructed PD models by methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) or MPP⁺ treatment. Then RT‐qPCR revealed that IGF‐1 expression was downregulated while iNOS expression was upregulated in MPTP model. Moreover, IGF‐1 elevation or iNOS depletion enhanced cell viability and blocked cell apoptosis. Rescue assay disclosed iNOS overexpression reversed the effect on viability and apoptosis mediated by IGF‐1 upregulation. Furthermore, IGF‐1 was identified to positively regulate miR‐302b‐5p which could target iNOS. MiR‐302b‐5p could abolish the inhibitory function IGF‐1 exerted on cell apoptosis and iNOS could counteract miR‐302b‐5p upregulation‐triggered inhibition on cell apoptosis as well. Besides, we observed the deficiency of miR‐302b‐5p improved the lesioned neurobehavior of MPTP‐treated mice. To sum up, present study proved that miR‐302b‐5p enhanced the neuroprotective effect of IGF‐1 in MPTP‐induced PD by regulating iNOS, recommending a novel therapeutic target for PD treatment.

中文翻译：

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通过调节诱导型一氧化氮合酶，MiR-302b-5p增强了IGF-1在甲基-4-苯基-1,2,3,6-四氢吡啶诱导的帕金森氏病中的神经保护作用。

帕金森氏病（PD）是一种神经退行性疾病，会导致神经元细胞受损。以前曾报道过胰岛素样生长因子（IGF）-1在某些疾病中起神经保护作用。一氧化氮（NO）也可以调节神经元细胞。然而，PD中IGF-1和NO的潜在机制仍然需要阐明。在本研究中，我们探讨了IGF-1与诱导型一氧化氮合酶（iNOS）在PD进展中的相互作用。我们首先通过甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）或MPP ⁺构建了PD模型治疗。然后，RT-qPCR显示在MPTP模型中，IGF-1的表达下调，而iNOS的表达上调。此外，IGF-1升高或iNOS耗竭可增强细胞活力并阻止细胞凋亡。救援试验显示，iNOS过表达逆转了由IGF-1上调介导的对生存力和凋亡的影响。此外，IGF-1被确认可以积极调控可能靶向iNOS的miR-302b-5p。MiR-302b-5p可以消除IGF-1对细胞凋亡的抑制功能，而iNOS也可以抵消miR-302b-5p上调触发的对细胞凋亡的抑制作用。此外，我们观察到miR-302b-5p的缺乏改善了MPTP处理的小鼠的损伤神经行为。总结一下，