电针调节小鼠肠道微生物群:术后认知功能障碍的一个潜在靶点。

Electroacupuncture modulates gut microbiota in mice: A potential target in postoperative cognitive dysfunction.

作者信息

Zhu Binbin, Zhou Yanling, Zhou Weijian, Chen Chunqu, Wang Jianhua, Xu Shujun, Wang Qinwen

机构信息

The Department of Radiology and Anesthesiology, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang Province, China.

Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Jiangbei District, China.

出版信息

Anat Rec (Hoboken). 2023 Dec;306(12):3131-3143. doi: 10.1002/ar.25065. Epub 2022 Sep 12.

Abstract

The detailed mechanism of inflammation in postoperative cognitive dysfunction (POCD) is unclear. This study aimed to determine whether electroacupuncture (EA) ameliorates POCD by modulating gut microbial dysbiosis. Compared to the control group, mice in the EA group were treated at the acupoints Zusanli (ST36), Quchi (L111), Baihui (GV20), and Dazhui (GV14) 1 week before appendectomy. Novel object recognition and the Morris water maze tests were used to assess learning and spatial reference memory deficits, whereas hippocampus samples and stool samples were collected for central inflammatory tests and 16S-rRNA sequencing of intestinal flora, respectively. In amyloid precursor protein/presenilin 1 (APP/PS1) mice, EA enhanced spatial memory and learning deficits. The fecal microbial community was altered in APP/PS1 mice in the absence of EA following surgery. Among them, Coprococcus and Bacteroidetes were more abundant in the EA groups than in the control groups; however, Actinobacteriota, Helicobacteraceae, and Escherichia/shigella constitute the minor bacterial colonization in the EA groups. Furthermore, we found a significant negative correlation between Firmicutes and escape latency (Pearson correlation coefficient - 0.551, p < 0.01) and positive correlation between Proteobacteria and escape latency (Pearson correlation coefficient 0.462, p < 0.05). Electron microscopy revealed signs of blood-brain barrier (BBB) impairments and immunofluorescence images showed glial cells activated in the hippocampus of APP/PS mice without EA, and serum diamine oxidase levels were increased in these mice; whereas EA treatment significantly relieved the above pathological changes. Our findings implied that EA decreases hippocampal inflammation of APP/PS1 by upregulating benificial  gut microbiota, reducing BBB and intestinal barrier dysfunction, thus alleviates postoperative cognitive dysfunction. This may provide a novel target in POCD management.

摘要

术后认知功能障碍(POCD)中炎症的详细机制尚不清楚。本研究旨在确定电针(EA)是否通过调节肠道微生物失调来改善POCD。与对照组相比,EA组小鼠在阑尾切除术前1周于足三里(ST36)、曲池(LI11)、百会(GV20)和大椎(GV14)穴位进行治疗。采用新物体识别和莫里斯水迷宫试验评估学习和空间参考记忆缺陷,同时分别采集海马样本和粪便样本进行中枢炎症检测和肠道菌群16S-rRNA测序。在淀粉样前体蛋白/早老素1(APP/PS1)小鼠中,EA改善了空间记忆和学习缺陷。术后未进行EA治疗的APP/PS1小鼠粪便微生物群落发生改变。其中,EA组的粪球菌和拟杆菌比对照组更丰富;然而,放线菌门、螺杆菌科和埃希氏菌属/志贺氏菌属在EA组中构成次要细菌定植。此外,我们发现厚壁菌门与逃避潜伏期之间存在显著负相关(皮尔逊相关系数-0.551,p<0.01),变形菌门与逃避潜伏期之间存在正相关(皮尔逊相关系数0.462,p<0.05)。电子显微镜显示血脑屏障(BBB)受损迹象,免疫荧光图像显示未进行EA治疗的APP/PS小鼠海马中的胶质细胞被激活,这些小鼠的血清二胺氧化酶水平升高;而EA治疗显著缓解了上述病理变化。我们的研究结果表明,EA通过上调有益肠道微生物群、减少BBB和肠道屏障功能障碍来减轻APP/PS1小鼠的海马炎症,从而缓解术后认知功能障碍。这可能为POCD的管理提供一个新的靶点。

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