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四逆汤通过调节肠道微生物群落组成改善脓毒症小鼠的相关肺损伤。

Sini decoction ameliorates interrelated lung injury in septic mice by modulating the composition of gut microbiota.

机构信息

School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211000, PR China.

Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 211000, PR China.

出版信息

Microb Pathog. 2020 Mar;140:103956. doi: 10.1016/j.micpath.2019.103956. Epub 2019 Dec 28.

Abstract

Our work used cecal ligation and puncture (CLP) mice model and 16S rDNA sequencing to explore whether the therapeutic mechanism of Sini Decoction (SND) on sepsis was related to the intestinal flora currently of concern. Twenty-four hours after surgery, tissues and serum from three groups (Control, CLP and CLP + SND) were collected for further analysis and colon contents were isolated for 16S rDNA analysis. Mortality, histological examination and inflammatory cytokines levels confirmed that the sepsis model was induced successfully and resulted in serious pathological damage, while all of these could be reversed by SND. In intestinal flora analysis, the microbial richness and abundance were recovered after SND treatment. Furthermore, at the phylum level, the abundance of Proteobacteria showed drastic increase after CLP. Similarly, CLP surgery significantly disrupted the balance of intestinal flora, with a huge increase of Escherichia-Shigella, a Gram-negative genus that might release lipopolysaccharide (LPS) and other genera. And these shifts could be defused by SND, indicating its function of regulating gut microbiota. This study demonstrates that SND could ameliorate the symptoms and pathology associated with sepsis in CLP model via modulating the flora in intestinal tract, which enriches a possible mechanism of SND's therapeutic effect.

摘要

我们的工作使用盲肠结扎穿孔(CLP)小鼠模型和 16S rDNA 测序来探索四逆汤(SND)对脓毒症的治疗机制是否与当前关注的肠道菌群有关。手术后 24 小时,收集三组(对照组、CLP 组和 CLP+SND 组)的组织和血清进行进一步分析,并分离结肠内容物进行 16S rDNA 分析。死亡率、组织学检查和炎症细胞因子水平证实成功诱导了脓毒症模型,并导致严重的病理损伤,而 SND 可逆转所有这些损伤。在肠道菌群分析中,SND 治疗后微生物丰富度和丰度得到恢复。此外,在门水平上,CLP 后厚壁菌门的丰度明显增加。同样,CLP 手术显著破坏了肠道菌群的平衡,导致革兰氏阴性菌埃希氏菌-志贺氏菌大量增加,可能释放脂多糖(LPS)和其他属。而 SND 可以缓解这些变化,表明其调节肠道微生物群的功能。这项研究表明,SND 可以通过调节肠道菌群来改善 CLP 模型中与脓毒症相关的症状和病理,这丰富了 SND 治疗效果的可能机制。

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