Zheng X, Zhao Z, Zhao L
Department of Divine Medicine, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China.
Physiol Res. 2024 Mar 11;73(1):139-155. doi: 10.33549/physiolres.935168.
Nonsteroidal anti-inflammatory drugs are the most widely used drugs for Parkinson's disease (PD), of which ibuprofen shows positive effects in suppressing symptoms; however, the associated risk needs to be addressed in different pathological stages. Initially, we developed an initial and advanced stage of the Parkinson disease mouse model by intraperitoneal injection of MPTP (20 mg/kg; 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine) for 10 and 20 days, respectively. Subsequently, ibuprofen treatment was administered for 2 months, and a pole test, rotarod test, histology, immunohistochemistry, and western blotting were performed to determine neuronal motor function. Histological analysis for 10 days after mice were injected with MPTP showed the onset of neurodegeneration and cell aggregation, indicating the initial stages of Parkinson's disease. Advanced Parkinson's disease was marked by Lewy body formation after another 10 days of MPTP injection. Neurodegeneration reverted after ibuprofen therapy in initial Parkinson's disease but not in advanced Parkinson's disease. The pole and rotarod tests confirmed that motor activity in the initial Parkinson disease with ibuprofen treatment recovered (p<0.01). However, no improvement was observed in the ibuprofen-treated mice with advanced disease mice. Interestingly, ibuprofen treatment resulted in a significant improvement (p<0.01) in NURR1 (Nuclear receptor-related 1) expression in mice with early PD, but no substantial improvement was observed in its expression in mice with advanced PD. Our findings indicate that NURR1 exerts anti-inflammatory and neuroprotective effects. Overall, NURR1 contributed to the effects of ibuprofen on PD at different pathological stages.
非甾体抗炎药是治疗帕金森病（PD）最广泛使用的药物，其中布洛芬在抑制症状方面显示出积极作用；然而，在不同病理阶段相关风险需要加以关注。最初，我们通过分别腹腔注射MPTP（20mg/kg；1-甲基-4-苯基-1,2,3,6-四氢吡啶）10天和20天，建立了帕金森病小鼠的初期和晚期模型。随后，给予布洛芬治疗2个月，并进行爬杆试验、转棒试验、组织学、免疫组织化学和蛋白质印迹分析以确定神经元运动功能。小鼠注射MPTP后10天的组织学分析显示神经退行性变和细胞聚集开始，表明处于帕金森病的初期阶段。在MPTP注射另外10天后，晚期帕金森病以路易小体形成为特征。布洛芬治疗后，初期帕金森病的神经退行性变得到逆转，但晚期帕金森病未得到逆转。爬杆试验和转棒试验证实，布洛芬治疗的初期帕金森病小鼠的运动活性恢复（p<0.01）。然而，在布洛芬治疗的晚期疾病小鼠中未观察到改善。有趣的是，布洛芬治疗使早期PD小鼠的NURR1（核受体相关因子1）表达有显著改善（p<0.01），但在晚期PD小鼠中其表达未观察到实质性改善。我们的研究结果表明，NURR1具有抗炎和神经保护作用。总体而言，NURR1在不同病理阶段促成了布洛芬对PD的作用。
