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葡萄糖依赖性胰岛素多肽减轻帕金森病大鼠中 6-OHDA 诱导的行为损伤。

Glucose-Dependent Insulinotropic Polypeptide Mitigates 6-OHDA-Induced Behavioral Impairments in Parkinsonian Rats.

机构信息

The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.

Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 11031, Taiwan.

出版信息

Int J Mol Sci. 2018 Apr 11;19(4):1153. doi: 10.3390/ijms19041153.

DOI:10.3390/ijms19041153
PMID:29641447
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5979480/
Abstract

In the present study, the effectiveness of glucose-dependent insulinotropic polypeptide (GIP) was evaluated by behavioral tests in 6-hydroxydopamine (6-OHDA) hemi-parkinsonian (PD) rats. Pharmacokinetic measurements of GIP were carried out at the same dose studied behaviorally, as well as at a lower dose used previously. GIP was delivered by subcutaneous administration (s.c.) using implanted ALZET micro-osmotic pumps. After two days of pre-treatment, male Sprague Dawley rats received a single unilateral injection of 6-OHDA into the medial forebrain bundle (MFB). The neuroprotective effects of GIP were evaluated by apomorphine-induced contralateral rotations, as well as by locomotor and anxiety-like behaviors in open-field tests. Concentrations of human active and total GIP were measured in plasma during a five-day treatment period by ELISA and were found to be within a clinically translatable range. GIP pretreatment reduced behavioral abnormalities induced by the unilateral nigrostriatal dopamine (DA) lesion produced by 6-OHDA, and thus may be a novel target for PD therapeutic development.

摘要

在本研究中，通过行为测试评估了葡萄糖依赖性胰岛素释放肽（GIP）在 6-羟基多巴胺（6-OHDA）半帕金森病（PD）大鼠中的作用。在进行行为学研究的相同剂量以及之前使用的较低剂量下，进行了 GIP 的药代动力学测量。GIP 通过植入的 ALZET 微型渗透泵进行皮下给药（s.c.）。经过两天的预处理，雄性 Sprague Dawley 大鼠接受单侧内侧前脑束（MFB）6-OHDA 单次注射。通过阿扑吗啡诱导的对侧旋转以及在开放场测试中的运动和焦虑样行为来评估 GIP 的神经保护作用。在五天的治疗期间，通过 ELISA 测量血浆中人源活性和总 GIP 的浓度，发现其处于临床可转化的范围内。GIP 预处理可减轻由 6-OHDA 引起的单侧黑质纹状体多巴胺（DA）损伤诱导的行为异常，因此可能是 PD 治疗开发的新靶点。

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