Abstract：
Parkinson\'s disease (PD) is characterised by severe movement defects and the degeneration of dopaminergic neurones in the midbrain. The symptoms of PD can be managed with dopamine replacement therapy using L-3, 4-dihydroxyphenylalanine (L-dopa), which is the gold standard therapy for PD. However, long-term treatment with L-dopa can lead to motor complications. The central renin-angiotensin system (RAS) is associated with the development of neurodegenerative diseases in the brain. However, the role of the RAS in dopamine replacement therapy for PD remains unclear. Here, we tested the co-treatment of the angiotensin-converting enzyme inhibitor (ACEI) with L-dopa altered L-dopa-induced dyskinesia (LID) in a 6-hydroxydopamine (6-OHDA)-lesioned mouse model of PD. Perindopril, captopril, and enalapril were used as ACEIs. The co-treatment of ACEI with L-dopa significantly decreased LID development in 6-OHDA-lesioned mice. In addition, the astrocyte and microglial transcripts involving Ccl2, C3, Cd44, and Iigp1 were reduced by co-treatment with ACEI and L-dopa in the 6-OHDA-lesioned striatum. In conclusion, co-treatment with ACEIs and L-dopa, such as perindopril, captopril, and enalapril, may mitigate the severity of L-DOPA-induced dyskinesia in a mouse model of PD.
摘要：
帕金森病（PD）的特征是严重的运动缺陷和中脑多巴胺能神经元的变性。PD的症状可以通过使用L-3，4-二羟基苯丙氨酸（L-dopa）的多巴胺替代疗法来管理，这是PD的黄金标准疗法。然而,长期使用左旋多巴治疗可导致运动并发症.中央肾素-血管紧张素系统（RAS）与大脑中神经退行性疾病的发展有关。然而,RAS在多巴胺替代治疗PD中的作用尚不清楚.这里,我们在6-羟基多巴胺(6-OHDA)损伤的PD小鼠模型中,测试了血管紧张素转换酶抑制剂(ACEI)与左旋多巴改变的左旋多巴诱导的运动障碍(LID)的共同治疗.培多普利,卡托普利,依那普利被用作ACEI。ACEI与左旋多巴的共同治疗显着降低了6-OHDA病变小鼠的LID发育。此外,在6-OHDA损伤的纹状体中,通过与ACEI和L-多巴共同治疗,涉及Ccl2,C3,Cd44和Iigp1的星形胶质细胞和小胶质细胞转录本减少.总之,与ACEI和左旋多巴共同治疗，如培多普利，卡托普利,和依那普利,可以减轻PD小鼠模型中L-DOPA诱导的运动障碍的严重程度。
