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富含生长因子的血浆（PRGF）破坏 5XFAD 小鼠大脑中的血脑屏障完整性并增加淀粉样蛋白病理学。

Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice.

机构信息

Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA.

Health Science Center, LSU Department of Family Medicine, Shreveport, LA 71103, USA.

出版信息

Int J Mol Sci. 2019 Mar 25;20(6):1489. doi: 10.3390/ijms20061489.

DOI:10.3390/ijms20061489
PMID:30934587
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6471393/
Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting 5.4 million people in the United States. Currently approved pharmacologic interventions for AD are limited to symptomatic improvement, not affecting the underlying pathology. Therefore, the search for novel therapeutic strategies is ongoing. A hallmark of AD is the compromised blood-brain barrier (BBB); thus, developing drugs that target the BBB to enhance its integrity and function could be a novel approach to prevent and/or treat AD. Previous evidence has shown the beneficial effects of growth factors in the treatment of AD pathology. Based on reported positive results obtained with the product Endoret, the objective of this study was to investigate the effect of plasma rich in growth factors (PRGF) on the BBB integrity and function, initially in a cell-based BBB model and in 5x Familial Alzheimer's Disease (5xFAD) mice. Our results showed that while PRGF demonstrated a positive effect in the cell-based BBB model with the enhanced integrity and function of the model, the in-vivo findings showed that PRGF exacerbated amyloid pathology in 5xFAD brains. At 10 and 100% doses, PRGF increased amyloid deposition associated with increased apoptosis and neuroinflammation. In conclusion, our results suggest PRGF may not provide beneficial effects against AD and the consideration to utilize growth factors should further be investigated.

摘要

阿尔茨海默病（AD）是影响美国 540 万人的最常见神经退行性疾病。目前批准的 AD 药物治疗仅限于症状改善，不能影响潜在的病理。因此，正在寻找新的治疗策略。AD 的一个标志是血脑屏障（BBB）受损；因此，开发靶向 BBB 的药物以增强其完整性和功能可能是预防和/或治疗 AD 的一种新方法。先前的证据表明生长因子在治疗 AD 病理方面具有有益作用。基于 Endoret 产品的报告阳性结果，本研究的目的是研究富含生长因子的血浆（PRGF）对 BBB 完整性和功能的影响，最初是在基于细胞的 BBB 模型中和在 5x 家族性阿尔茨海默病（5xFAD）小鼠中进行研究。我们的结果表明，虽然 PRGF 在基于细胞的 BBB 模型中显示出积极的效果，增强了模型的完整性和功能，但体内研究结果表明 PRGF 加重了 5xFAD 大脑中的淀粉样蛋白病理。在 10%和 100%剂量下，PRGF 增加了与细胞凋亡和神经炎症增加相关的淀粉样蛋白沉积。总之，我们的结果表明 PRGF 可能不能提供对 AD 的有益作用，应进一步考虑使用生长因子。

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