Gastrointestinal Non-Motor Dysfunction in Parkinson's Disease Model Rats with 6-hydroxydopamine
Gastrointestinal Non-Motor Dysfunction in Parkinson's Disease Model Rats with 6-hydroxydopamine
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DOI：
10.33549/physiolres.933995
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发表时间：
2019-01-01
影响因子：
2.1
通讯作者：
Zhu, Jin-Xia
中科院分区：
文献类型：
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作者：
Feng, Xiao-Yan;Yan, Jing-Ting;Zhu, Jin-Xia
帕金森病（Parkinson's disease，PD）是一种以中脑黑质多巴胺能神经元的进行性缺失为特征的神经退行性疾病。为了进一步评价其病理生理学，需要准确的动物模型。本研究旨在验证6-羟基多巴胺（6-OHDA）双侧微量注射到SN对大鼠胃肠道症状的影响，并证实6-OHDA大鼠模型是研究帕金森病GI疾病机制的适当工具。本研究采用免疫组化、数字X线成像、短路电流、FITC-葡聚糖通透性和超高效液相色谱串联质谱法。结果表明，6-OHDA大鼠黑质内多巴胺能神经元和纹状体内多巴胺能纤维明显减少。6-OHDA大鼠在转棒试验中表现出占用减少，每日食物残渣增加，但体重或每日消耗量无差异。与对照组相比，6-OHDA大鼠粪便颗粒及其含量显著减少，胃排空和肠转运延迟。模型中体内FITC-葡聚糖渗透性增加和肠跨上皮阻力降低表明PD模型中消化道屏障功能减弱。此外，血浆中的炎症因子显示，促炎因子IL-1 β和IL-8在6-OHDA大鼠中显著增加。总的来说，这些研究结果表明，该模型是一个有趣的实验工具，以调查参与PD胃肠道功能障碍的进展机制。
Parkinson's disease (PD) is a neurodegenerative disease with a progressive loss of mesencephalic dopaminergic neurons of the substantia nigra (SN). To further evaluate its pathophysiology, accurate animal models are needed. The current study aims to verify the impact of a 6-hydroxydopamine (6-OHDA) bilateral microinjection into the SN on gastrointestinal symptoms in rats and confirm that the 6-OHDA rat model is an appropriate tool to investigate the mechanisms of Parkinsonian GI disorders. Immunohistochemistry, digital X-ray imaging, short-circuit current, FITC-dextran permeability and ultra-performance liquid chromatography tandem mass spectrometry were used in this study. The results indicated that the dopaminergic neurons in SN and fibres in the striatum were markedly reduced in 6-OHDA rats. The 6-OHDA rats manifested reductions in occupancy in a rotarod test and increases in daily food debris but no difference in body mass or daily consumption. Compared with control rats, faecal pellets and their contents were significantly decreased, whereas gastric emptying and intestinal transport were delayed in 6-OHDA rats. The increased in vivo FITC-dextran permeability and decreased intestinal transepithelial resistance in the model suggest attenuated barrier function in the digestive tract in the PD model. Moreover, inflammatory factors in the plasma showed that pro-inflammatory factors IL-1 beta and IL-8 were significantly increased in 6-OHDA rats. Collectively, these findings indicate that the model is an interesting experimental tool to investigate the mechanisms involved in the progression of gastrointestinal dysfunction in PD.