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醋酸盐下调支气管肺发育不良新生小鼠中NLRP3炎性小体的激活并减轻肺损伤。

Acetate Downregulates the Activation of NLRP3 Inflammasomes and Attenuates Lung Injury in Neonatal Mice With Bronchopulmonary Dysplasia.

作者信息

Zhang Qian, Ran Xiao, He Yu, Ai Qing, Shi Yuan

机构信息

Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.

Chongqing Key Laboratory of Pediatrics, Chongqing, China.

出版信息

Front Pediatr. 2021 Feb 4;8:595157. doi: 10.3389/fped.2020.595157. eCollection 2020.

DOI:10.3389/fped.2020.595157
PMID:33614540
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7889800/
Abstract

Bronchopulmonary dysplasia (BPD) is a common pulmonary complication in preterm infants. Acetate is a metabolite produced by the gut microbiota, and its anti-inflammatory function is well known. The role of acetate in BPD has not been studied. Here, we investigate the effects of acetate on lung inflammation and damage in mice model of BPD. To investigate the role of acetate in the development of BPD. C57BL/6 mice were randomly divided into three groups on the 3rd day after birth: room air group, hyperoxia group, and hyperoxia + acetate (250 mM, 0.02 ml/g) group. The expression of inflammatory factors was determined by ELISA and RT-PCR, and NLRP3 and caspase-1 were detected by Western blot. High-throughput sequencing was used to detect bacterial communities in the mice intestines. After acetate treatment, the expression levels of TNF-α, IL-1β, IL-18, NLRP3, and caspase-1 were significantly reduced, while the expression of GPR43 was increased. In the BPD mice treated with acetate, the proportion of Escherichia-Shigella was lower than in placebo-treated BPD mice, while the abundance of Ruminococcus was increased. These results indicate that acetate may regulate intestinal flora and reduce inflammatory reactions and lung injury in BPD. Therefore, acetate may be an effective drug to protect against neonatal BPD.

摘要

支气管肺发育不良(BPD)是早产儿常见的肺部并发症。乙酸盐是肠道微生物群产生的一种代谢产物,其抗炎功能众所周知。乙酸盐在BPD中的作用尚未得到研究。在此,我们研究了乙酸盐对BPD小鼠模型肺部炎症和损伤的影响。为了研究乙酸盐在BPD发生发展中的作用。将C57BL/6小鼠在出生后第3天随机分为三组:常氧组、高氧组和高氧+乙酸盐(250 mM,0.02 ml/g)组。通过ELISA和RT-PCR测定炎症因子的表达,并通过蛋白质印迹法检测NLRP3和半胱天冬酶-1。采用高通量测序检测小鼠肠道中的细菌群落。乙酸盐处理后,TNF-α、IL-1β、IL-18、NLRP3和半胱天冬酶-1的表达水平显著降低,而GPR43的表达增加。在用乙酸盐治疗的BPD小鼠中,大肠埃希菌-志贺菌属的比例低于安慰剂治疗的BPD小鼠,而瘤胃球菌的丰度增加。这些结果表明,乙酸盐可能调节肠道菌群,减少BPD中的炎症反应和肺损伤。因此,乙酸盐可能是预防新生儿BPD的有效药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5675/7889800/3480a49bbf40/fped-08-595157-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5675/7889800/c4c979adef29/fped-08-595157-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5675/7889800/25bd3525ca91/fped-08-595157-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5675/7889800/a1ff1a1d3539/fped-08-595157-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5675/7889800/fe69082c64ab/fped-08-595157-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5675/7889800/3480a49bbf40/fped-08-595157-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5675/7889800/c4c979adef29/fped-08-595157-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5675/7889800/25bd3525ca91/fped-08-595157-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5675/7889800/a1ff1a1d3539/fped-08-595157-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5675/7889800/fe69082c64ab/fped-08-595157-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5675/7889800/3480a49bbf40/fped-08-595157-g0005.jpg

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