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耐力运动训练可防止 MPTP/丙磺舒诱导的帕金森病小鼠模型纹状体中一氧化氮的上调。

Endurance exercise training protects against the upregulation of nitric oxide in the striatum of MPTP/probenecid mouse model of Parkinson's disease.

机构信息

Department of Rehabilitation Sciences, Jordan University of Science and Technology JUST, 22110 Irbid, Jordan.

出版信息

NeuroRehabilitation. 2013;32(1):141-7. doi: 10.3233/NRE-130831.

Abstract

OBJECTIVES

Parkinson's disease (PD) is a neurodegenerative disorder, caused by the gradual loss of cells in substantia nigra. Nitric oxide (NO) plays an important role in a variety of signal transduction pathways that are crucial for maintaining the physiologic functions of nervous system. The aims of this study are: 1) To investigate the expression of the inducible form of NO (iNOS), and compare it to neuronal nitric oxide (nNOS) in the brain of a chronic mouse model of PD and 2) To study the effect of endurance exercise training on the expression of these markers.

METHOD

Mouse models of PD were obtained using 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. Forty C57BL /6 albino mice were randomly divided into four groups: sedentary control (SC, N = 10), exercise control (EC, N = 10), sedentary PD (SPD, N = 10), exercise PD (EPD, N = 10). At the end of training program, nNOS and iNOS were evaluated in the striatum in all animal groups using immunohistochemistry.

RESULTS

nNOS showed significant increases in striatum (ST) of SPD mice compared to SC mice (P > 0.03). There was also decreased expression of nNOS in EC group compared to SC mice, but this decrease was not significant (P > 0.8). Exercise training significantly decreased the level of nNOS in the EPD compared to SPD, (P > 0.04). Although, iNOS expression followed almost the same trend as nNOS, but exercise training did not significantly decrease the expression of iNOS in both EC and EPD groups, P > 0.2 and 0.3 respectively.

DISCUSSION

The data from this study suggests that 4 weeks of treadmill exercise has a positive impact on the expression of nNOS and iNOS in the striatum of a PD model. This might clear in part the pathogenicity of the diseases and the positive impact of training on PD.

摘要

目的

帕金森病(PD)是一种神经退行性疾病,由黑质细胞逐渐丧失引起。一氧化氮(NO)在多种信号转导途径中发挥重要作用,这些途径对维持神经系统的生理功能至关重要。本研究的目的是:1)研究诱导型一氧化氮合酶(iNOS)的表达,并将其与 PD 慢性小鼠模型中的神经元型一氧化氮合酶(nNOS)进行比较;2)研究耐力运动训练对这些标志物表达的影响。

方法

使用 10 次 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)(25mg/kg)和丙磺舒(250mg/kg)对 C57BL/6 白化鼠进行 PD 小鼠模型的制备,持续 5 周。40 只 C57BL/6 白化鼠随机分为 4 组:安静对照组(SC,N=10)、运动对照组(EC,N=10)、安静 PD 组(SPD,N=10)、运动 PD 组(EPD,N=10)。在训练计划结束时,使用免疫组织化学法评估所有动物组纹状体中的 nNOS 和 iNOS。

结果

与 SC 组相比,SPD 组小鼠纹状体(ST)中的 nNOS 表达显著增加(P>0.03)。与 SC 组相比,EC 组 nNOS 的表达也有所降低,但差异无统计学意义(P>0.8)。与 SPD 组相比,EPD 组 nNOS 的水平显著降低(P>0.04)。虽然 iNOS 的表达趋势与 nNOS 相似,但在 EC 和 EPD 组中,运动训练并没有显著降低 iNOS 的表达,P>0.2 和 P>0.3 分别。

讨论

本研究的数据表明,4 周的跑步机运动对 PD 模型纹状体中 nNOS 和 iNOS 的表达有积极影响。这可能部分阐明了疾病的发病机制以及训练对 PD 的积极影响。

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