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[认知障碍早产大鼠肠道菌群的结构特征:基于高通量测序的分析]

[Structural features of intestinal flora in preterm rats with cognitive impairment: an analysis based on high-thorough sequencing].

作者信息

Yue Tao, Lu Hong-Yan, Xue Zheng-Yang, Xu Su-Qing, Tang Wei

机构信息

Department of Pediatrics, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2019 Jul;21(7):701-707. doi: 10.7499/j.issn.1008-8830.2019.07.016.

Abstract

OBJECTIVE

To study the structural features of intestinal flora in preterm rats with cognitive impairment and the association of the change in intestinal flora with cognitive impairment in preterm rats.

METHODS

Sprague-Dawley rats at 16-17 days of gestation were intraperitoneally injected with lipopolysaccharide for two consecutive days to establish a model of cognitive impairment, and the rats treated with intraperitoneally injected phosphate-buffered saline were established as the control group. Cesarean section was performed on day 21 of gestation, and preterm rats were randomly assigned to healthy maternal rats for feeding. The place navigation test in the Morris water maze was used to evaluate cognition on day 30 after birth. According to the result, the preterm rats were divided into cognitive impairment group with 21 rats and normal control group with 10 rats. Hematoxylin and eosin staining was used to observe pathological changes of the hippocampus, and fecal samples were collected for 16S rRNA sequencing and analysis. A principal component analysis (PCA) was performed for intestinal flora.

RESULTS

Compared with the normal control group, the cognitive impairment group showed degeneration and necrosis of a large number of neurons in the hippocampus. Compared with the normal control group, the cognitive impairment group had significant reductions in the abundance and diversity of intestinal flora (P<0.05), with a significant increase in the abundance of Proteobacteria at the phylum level (P<0.05), as well as significant reductions in the abundance of Prevotella and Lactobacillus and significant increases in the abundance of Staphylococcaceae and Oligella at the order, family, and genus levels (P<0.05). PCA showed a significant difference in the composition of intestinal flora between the two groups.

CONCLUSIONS

There is a significant change in the structure of intestinal flora in preterm rats with cognitive impairment, which provides a basis for the treatment and intervention of microecological changes due to cognitive impairment after preterm birth.

摘要

目的

研究认知功能障碍早产大鼠肠道菌群的结构特征以及肠道菌群变化与早产大鼠认知功能障碍的关系。

方法

将妊娠16 - 17天的斯普拉格-道利大鼠连续两天腹腔注射脂多糖以建立认知功能障碍模型,将腹腔注射磷酸盐缓冲液的大鼠作为对照组。在妊娠第21天进行剖宫产,将早产大鼠随机分配给健康母鼠喂养。在出生后第30天,采用Morris水迷宫中的位置导航试验评估认知功能。根据结果,将早产大鼠分为认知功能障碍组(21只)和正常对照组(10只)。采用苏木精-伊红染色观察海马体的病理变化,并收集粪便样本进行16S rRNA测序和分析。对肠道菌群进行主成分分析(PCA)。

结果

与正常对照组相比,认知功能障碍组海马体中有大量神经元变性和坏死。与正常对照组相比,认知功能障碍组肠道菌群的丰度和多样性显著降低(P<0.05),在门水平上变形菌门的丰度显著增加(P<0.05),在目、科和属水平上普雷沃氏菌属和乳杆菌属的丰度显著降低,葡萄球菌科和寡养单胞菌属的丰度显著增加(P<0.05)。PCA显示两组肠道菌群组成存在显著差异。

结论

认知功能障碍早产大鼠肠道菌群结构发生显著变化,为早产出生后认知功能障碍所致微生态变化的治疗和干预提供了依据。

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本文引用的文献

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Early neurodevelopmental outcomes of extremely preterm infants.极早早产儿的早期神经发育结局
Semin Perinatol. 2016 Dec;40(8):497-509. doi: 10.1053/j.semperi.2016.09.002. Epub 2016 Nov 16.
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Proteobacteria: microbial signature of dysbiosis in gut microbiota.变形菌门:肠道微生物失调的微生物特征。
Trends Biotechnol. 2015 Sep;33(9):496-503. doi: 10.1016/j.tibtech.2015.06.011. Epub 2015 Jul 22.

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