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肠道菌群靶向光生物调节疗法改善 Aβ诱导的阿尔茨海默病动物模型中的老年痴呆症。

Gut flora-targeted photobiomodulation therapy improves senile dementia in an Aß-induced Alzheimer's disease animal model.

机构信息

Laser Medicine Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China; Beijing Key Laboratory of Rehabilitation Technical Aids for Old-Age Disability, National Research Center for Rehabilitation Technical Aids, Beijing 100176, China.

Laser Medicine Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China.

出版信息

J Photochem Photobiol B. 2021 Mar;216:112152. doi: 10.1016/j.jphotobiol.2021.112152. Epub 2021 Feb 10.

Abstract

BACKGROUND

Emerging evidence suggests that the gut microbiota plays an important role in the pathological progression of Alzheimer's disease (AD). Photobiomodulation (PBM) therapy is believed to have a positive regulatory effect on the imbalance of certain body functions, including inflammation, immunity, wound healing, nerve repair, and pain. Previous studies have found that the intestinal flora of patients with AD is in an unbalanced state. Therefore, we have proposed the use of gut flora-targeted PBM (gf-targeted PBM) as a method to improve AD in an Aß-induced AD mouse model.

METHODS

PBM was performed on the abdomen of the mice at the wavelengths of 630 nm, 730 nm, and 850 nm at 100 J/cm for 8 weeks. Morris water maze test, immunofluorescence and proteomic of hippocampus, and intestinal flora detection of fecal were used to evaluate the treatment effects of gf-targeted PBM on AD rats.

RESULTS

PBM at all three wavelengths (especially 630 nm and 730 nm) significantly improved learning retention as measured by the Morris water maze. In addition, we found reduced amyloidosis and tau phosphorylation in the hippocampus by immunofluorescence in AD mice. By using a quantitative proteomic analysis of the hippocampus, we found that gf-targeted PBM significantly altered the expression levels of 509 proteins (the same differentially expressed proteins in all three wavelengths of PBM), which involved the pathways of hormone synthesis, phagocytosis, and metabolism. The 16 s rRNA gene sequencing of fecal contents showed that PBM significantly altered the diversity and abundance of intestinal flora. Specifically, PBM treatment reversed the typical increase of Helicobacter and uncultured Bacteroidales and the decrease of Rikenella seen in AD mice.

CONCLUSIONS

Our data indicate that gf-targeted PBM regulates the diversity of intestinal flora, which may improve damage caused by AD. Gf-targeted PBM has the potential to be a noninvasive microflora regulation method for AD patients.

摘要

背景

越来越多的证据表明,肠道微生物群在阿尔茨海默病(AD)的病理进展中起着重要作用。光生物调节(PBM)疗法被认为对某些身体功能的失衡具有积极的调节作用,包括炎症、免疫、伤口愈合、神经修复和疼痛。先前的研究发现,AD 患者的肠道菌群处于失衡状态。因此,我们提出使用靶向肠道菌群的 PBM(gf-targeted PBM)作为改善 Aβ诱导的 AD 小鼠模型中 AD 的方法。

方法

在波长为 630nm、730nm 和 850nm 的条件下,对小鼠腹部进行 PBM,剂量为 100J/cm,共 8 周。使用 Morris 水迷宫测试、海马免疫荧光和蛋白质组学以及粪便肠道菌群检测来评估 gf-targeted PBM 对 AD 大鼠的治疗效果。

结果

所有三种波长(特别是 630nm 和 730nm)的 PBM 均显著改善了 AD 小鼠的Morris 水迷宫测试中的学习保留。此外,我们发现免疫荧光显示 PBM 可减少 AD 小鼠海马中的淀粉样蛋白沉积和 tau 磷酸化。通过对海马进行定量蛋白质组学分析,我们发现 gf-targeted PBM 显著改变了 509 种蛋白质的表达水平(三种波长的 PBM 中均存在相同的差异表达蛋白),这些蛋白质涉及激素合成、吞噬作用和代谢途径。粪便内容物的 16s rRNA 基因测序显示,PBM 显著改变了肠道菌群的多样性和丰度。具体而言,PBM 治疗可逆转 AD 小鼠中典型的 Helicobacter 和未培养拟杆菌增加以及 Rikenella 减少。

结论

我们的数据表明,gf-targeted PBM 调节肠道菌群的多样性,这可能改善 AD 引起的损伤。Gf-targeted PBM 有可能成为 AD 患者的非侵入性微生物群调节方法。

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