布洛芬的潜在神经保护作用：来自帕金森病小鼠模型的研究。

Potential neuroprotective effect of ibuprofen, insights from the mice model of Parkinson's disease.

机构信息

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Krakowskie Przedmieście 26/28, PL 00-927 Warszawa, Poland.

出版信息

Pharmacol Rep. 2013;65(5):1227-36. doi: 10.1016/s1734-1140(13)71480-4.

DOI:10.1016/s1734-1140(13)71480-4

PMID:24399718

Abstract

BACKGROUND

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. An inflammatory reaction seems to be involved in the pathological process in PD. Prospective clinical studies with various nonsteroidal anti-inflammatory drugs (NSAIDs) have shown that ibuprofen decreases the risk of PD. In the present study we investigated the influence of ibuprofen on dopaminergic neuron injury in the mice model of PD.

METHODS

Twelve-month-old male C57Bl mice were injected with MPTP together with various doses of ibuprofen (10, 30 or 50 mg/kg), administered 1 h before MPTP injection for 7 consecutive days. Evaluation concerned dopamine content in the striatum, tyrosine hydroxylase (TH) protein and α-synuclein expression measured 7 and 21 days post MPTP administration (dpa).

RESULTS

MPTP caused injury to dopaminergic neuron endings in the striatum: dopamine content decreased by about 0% 7 dpa and by 85% 21 dpa; TH protein expression diminished by 21% 7 dpa; α-synuclein level decreased by 10 and 26% 7 and 21 dpa, respectively. Ibuprofen administration to mice treated with MPTP significantly increased the level of dopamine in the striatum 7 and 21 dpa. It also prevented TH protein decrease and increased α-synuclein level 21 dpa.

CONCLUSIONS

Ibuprofen was shown to protect neurons against MPTP-induced injury in the striatum. The possible mechanism of the neuroprotective effect of ibuprofen might be associated with decreased dopamine turnover and cyclooxygenases inhibition resulting in lower reactive oxygen species formation.

摘要

背景

帕金森病（PD）是最常见的神经退行性疾病之一。炎症反应似乎参与了 PD 的病理过程。各种非甾体抗炎药（NSAIDs）的前瞻性临床研究表明，布洛芬可降低 PD 的发病风险。在本研究中，我们研究了布洛芬对 PD 小鼠模型中多巴胺能神经元损伤的影响。

方法

12 月龄雄性 C57Bl 小鼠接受 MPTP 联合不同剂量布洛芬（10、30 或 50mg/kg）注射，于 MPTP 注射前 1 小时连续 7 天给药。评估指标包括纹状体中的多巴胺含量、酪氨酸羟化酶（TH）蛋白和α-突触核蛋白表达，分别在 MPTP 给药后 7 天和 21 天进行测量。

结果

MPTP 导致纹状体多巴胺能神经元末梢损伤：多巴胺含量在 7 天和 21 天分别下降约 0%和 85%；TH 蛋白表达在 7 天下降 21%；α-突触核蛋白水平在 7 天和 21 天分别下降 10%和 26%。给予 MPTP 处理的小鼠布洛芬治疗显著增加了纹状体中多巴胺的水平在 7 天和 21 天。它还防止了 TH 蛋白减少和增加了 21 天的α-突触核蛋白水平。