Yan Qingqing, Jia Lin, Wen Biyan, Wu Yao, Zeng Yanbo, Wang Qing
Department of Gastroenterology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.
Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
Front Pharmacol. 2022 Jul 18;13:919010. doi: 10.3389/fphar.2022.919010. eCollection 2022.
Evidence have shown that gut microbiota plays an important role in the development of severe acute pancreatitis (SAP). In addition, matrix metalloproteinase-9 (MMP9) plays an important role in intestinal injury in SAP. Thus, we aimed to determine whether gut microbiota could regulate the intestinal injury during SAP modulating MMP9. In this study, the fecal samples of patients with SAP ( = 72) and healthy controls ( = 32) were analyzed by 16S rRNA gene sequencing. In addition, to investigate the association between gut microbiota and MMP9 in intestinal injury during SAP, we established MMP9 stable knockdown Caco2 and HT29 cells and generated a MMP9 knockout (MMP9-/-) mouse model of SAP . We found that the abundance of (C. ) was significantly decreased in the SAP group. In addition, overexpression of MMP9 notably downregulated the expressions of tight junction proteins and upregulated the expressions of p-p38 and p-ERK in Caco2 and HT29 cells ( < 0.05). However, C. or butyrate treatment remarkably upregulated the expressions of tight junction proteins and downregulated the expressions of MMP9, p-p38 and p-ERK in MMP9-overexpressed Caco2 and HT29 cells ( < 0.05). Importantly, C. or butyrate could not affect the expressions of tight junction proteins, and MMP9, p-p38 and p-ERK proteins in MMP9-knockdown cells compared with MMP9-knockdown group. Consistently, C. or butyrate could not attenuate pancreatic and intestinal injury during SAP in MMP9-/- mice compared with the SAP group. Collectively, C. could protect against pancreatic and intestinal injury after SAP downregulation of MMP9 and .
证据表明，肠道微生物群在重症急性胰腺炎（SAP）的发展中起重要作用。此外，基质金属蛋白酶-9（MMP9）在SAP的肠道损伤中起重要作用。因此，我们旨在确定肠道微生物群是否可以通过调节MMP9来调控SAP期间的肠道损伤。在本研究中，通过16S rRNA基因测序分析了SAP患者（n = 72）和健康对照者（n = 32）的粪便样本。此外，为了研究SAP期间肠道微生物群与肠道损伤中MMP9之间的关联，我们建立了MMP9稳定敲低的Caco2和HT29细胞，并构建了MMP9基因敲除（MMP9-/-）的SAP小鼠模型。我们发现，SAP组中柯林斯菌（C.）的丰度显著降低。此外，MMP9的过表达显著下调了Caco2和HT29细胞中紧密连接蛋白的表达，并上调了p-p38和p-ERK的表达（P < 0.05）。然而，在MMP9过表达的Caco2和HT29细胞中，柯林斯菌或丁酸盐处理显著上调了紧密连接蛋白的表达，并下调了MMP9、p-p38和p-ERK的表达（P < 0.05）。重要的是，与MMP9敲低组相比，柯林斯菌或丁酸盐对MMP9敲低细胞中紧密连接蛋白以及MMP9、p-p38和p-ERK蛋白的表达没有影响。同样，与SAP组相比，柯林斯菌或丁酸盐在MMP9-/-小鼠的SAP期间不能减轻胰腺和肠道损伤。总体而言，柯林斯菌可通过下调MMP9来预防SAP后的胰腺和肠道损伤。
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