Fu Xiao-Xiao, Wang Jin, Cai Hua-Ying, Jiang Hong, Jiang Jin-Zhan, Chen Hao-Hao, Han Shu
Institute of Anatomy and Sir Run Run Shaw Hospital, Medical College, Zhejiang University, Hangzhou, People's Republic of China.
Medical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, Jinhua, People's Republic of China.
J Inflamm Res. 2022 Jul 7;15:3797-3814. doi: 10.2147/JIR.S368291. eCollection 2022.
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.
左旋多巴被视为帕金森病（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），这会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。
在帕金森病啮齿动物模型中评估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）与左旋多巴联合使用的治疗效果。
我们在由1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病啮齿动物模型中给予C16和Ang-1的组合。75只小鼠被随机分为五个治疗组：对照组、溶剂组、左旋多巴组、C16+Ang-1组和左旋多巴+C16+Ang-1组。采用行为学、组织学和电生理学实验来确定神经元功能和恢复情况。
结果表明，C16+Ang-1治疗减轻了中枢神经系统的神经炎症，并促进了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，并改善左旋多巴的效果。这种治疗策略未来可发展成为一种联合治疗方法。
