Co-Application of C16 and Ang-1 Improves the Effects of Levodopa in Parkinson Disease Treatment.
Co-Application of C16 and Ang-1 Improves the Effects of Levodopa in Parkinson Disease Treatment.
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DOI：
10.2147/jir.s368291
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发表时间：
2022
影响因子：
4.5
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中科院分区：
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左旋多巴被认为是帕金森病（PD）治疗的标准药物。然而，长期服用左旋多巴会导致左旋多巴诱导的运动障碍（LID），这可以显著影响患者的生活质量。先前的研究表明，大脑中的神经炎症在LID中起作用，并增加了与左旋多巴副作用相关的潜在神经炎症介质。C16（一种竞争性结合整合素αvβ3并抑制炎症细胞浸润的肽）和血管生成素-1 （Ang-1，一种对血管保护至关重要的血管内皮生长因子）以及左旋多巴的治疗效果在啮齿动物PD模型中进行了评估。我们在MPTP（1-甲基-4-苯基-1,2,3,6-四氢吡啶）诱导的PD啮齿动物模型中联合给予C16和Ang-1。将75只小鼠随机分为对照组、对照组、左旋多巴组、C16+Ang-1组和左旋多巴+C16+Ang-1组。行为学、组织学和电生理实验用于测定神经元功能和恢复情况。结果显示，C16+Ang-1治疗可减轻中枢神经系统炎症，促进左旋多巴对神经功能的恢复作用。我们的研究表明，C16+Ang-1可以弥补左旋多巴的不足，改善中枢神经系统微环境，改善左旋多巴的作用。这种治疗策略可以在未来发展为一种组合治疗。
Levodopa is regarded as a standard medication in Parkinson disease (PD) treatment. However, long-term administration of levodopa leads to levodopa-induced dyskinesia (LID), which can markedly affect patient quality of life. Previous studies have shown that neuroinflammation in the brain plays a role in LID and increases potential neuroinflammatory mediators associated with the side effects of levodopa. The treatment effect of C16 (a peptide that competitively binds integrin αvβ3 and inhibits inflammatory cell infiltration) and angiopoietin-1 (Ang-1; a vascular endothelial growth factor vital for blood vessel protection), along with levodopa, was evaluated in a rodent model of PD. We administered a combination of C16 and Ang-1 in a rodent model of PD induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Seventy-five mice were randomly divided into five treatment groups: control, vehicle, levodopa, C16+Ang-1, and levodopa+C16+Ang-1. Behavioral, histological, and electrophysiological experiments were used to determine neuron function and recovery. The results showed that C16+Ang-1 treatment alleviated neuroinflammation in the CNS and promoted the recovery effects of levodopa on neural function. Our study suggests that C16+Ang-1 can compensate for the shortcomings of levodopa, improve the CNS microenvironment, and ameliorate the effects of levodopa. This treatment strategy could be developed as a combinatorial therapeutic in the future.