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丙戊酸和丁酸盐对肠道屏障功能的影响:伴有腹腔内高压的重症急性胰腺炎大鼠模型的研究

Effect of and Butyrate on Intestinal Barrier Functions: Study of a Rat Model of Severe Acute Pancreatitis With Intra-Abdominal Hypertension.

作者信息

Zhao Han-Bing, Jia Lin, Yan Qing-Qing, Deng Qi, Wei Bo

机构信息

Department of Gastroenterology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.

Department of Clinical Medicine, Guizhou Medical University, Guiyang, China.

出版信息

Front Physiol. 2020 Oct 29;11:561061. doi: 10.3389/fphys.2020.561061. eCollection 2020.

Abstract

BACKGROUND/AIMS: Severe acute pancreatitis (SAP) is associated with intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS), but treatment of these conditions is difficult. We studied a rat model of SAP + IAH to determine the effect of oral administration of and butyrate (its major metabolite) on intestinal barrier functions.

METHODS

A total of 48 rats were assigned to four groups, with 12 rats per group: Sham, SAP+IAH, SAP+IAH+, and SAP + IAH + butyrate. SAP was induced by sodium taurocholate infusion into the biliopancreatic duct, intra-abdominal pressure (IAP), mortality was measured 24 h later, and then rats were euthanized. The plasma levels of several markers [amylase, diamine oxidase (DAO), fluorescein isothiocyanate (FITC)-dextran, tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, IL-12, lipopolysaccharide (LPS)] and fecal butyric acid level were determined. The pancreas and intestine were examined using histology, and RT-PCR and Western blotting of intestinal tissues were used to measure the expression of six markers {tight junction proteins [zonula occludens protein-1 (ZO-1), claudin-1, claudin-2, occluding], matrix metalloproteinase 9 [MMP9], and TNF-α}. The gut flora of the rats was examined by 16S rRNA sequencing.

RESULTS

Induction of SAP + IAH altered several functions of the intestinal barrier, and enhanced intestinal permeability, decreased the levels of ZO-1, claudin-1, occludin, the richness and diversity of the microflora community, the relative abundance (RA) of Firmicutes, and the number of probiotic organisms. However, induction of SAP+IAH increased the expression of claudin-2, MMP9, and TNF-α, and the RA of Proteobacteria and pathogens in the feces. Rats that received oral or butyrate had reduced intestinal injury and plasma levels of DAO, LPS, and inflammatory cytokines.

CONCLUSION

This study of rats with SAP+IAH indicated that oral dosing of or butyrate reduced intestinal injury, possibly by altering the functions of the intestinal mucosal barrier.

摘要

背景/目的:重症急性胰腺炎(SAP)与腹腔内高压(IAH)和腹腔间隔室综合征(ACS)相关,但这些病症的治疗很困难。我们研究了SAP + IAH大鼠模型,以确定口服和丁酸盐(其主要代谢产物)对肠道屏障功能的影响。

方法

总共48只大鼠被分为四组,每组12只:假手术组、SAP+IAH组、SAP+IAH+组和SAP + IAH +丁酸盐组。通过向胆胰管内注入牛磺胆酸钠诱导SAP,24小时后测量腹腔内压力(IAP)和死亡率,然后对大鼠实施安乐死。测定几种标志物的血浆水平[淀粉酶、二胺氧化酶(DAO)、异硫氰酸荧光素(FITC)-葡聚糖、肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6、IL-1β、IL-12、脂多糖(LPS)]以及粪便丁酸水平。使用组织学检查胰腺和肠道,并通过RT-PCR和Western印迹法检测肠道组织中六种标志物的表达{紧密连接蛋白[闭合蛋白-1(ZO-1)、闭合蛋白-1、闭合蛋白-2、闭合蛋白]、基质金属蛋白酶9[MMP9]和TNF-α}。通过16S rRNA测序检查大鼠的肠道菌群。

结果

诱导SAP + IAH改变了肠道屏障的多种功能,增强了肠道通透性,降低了ZO-1、闭合蛋白-1、闭合蛋白的水平、微生物群落的丰富度和多样性、厚壁菌门的相对丰度以及益生菌数量。然而,诱导SAP+IAH增加了闭合蛋白-2、MMP9和TNF-α的表达以及粪便中变形菌门和病原体的相对丰度。口服或丁酸盐的大鼠肠道损伤减轻,DAO、LPS和炎性细胞因子的血浆水平降低。

结论

这项对SAP+IAH大鼠的研究表明,口服或丁酸盐可减轻肠道损伤,可能是通过改变肠黏膜屏障的功能实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c1a/7658654/b5dd8170569e/fphys-11-561061-g001.jpg

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