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丁酸梭菌通过作用于 NLRP6 抑制结肠黏膜低度炎症,从而调节肠易激综合征内脏高敏感性。

Clostridium butyricum regulates visceral hypersensitivity of irritable bowel syndrome by inhibiting colonic mucous low grade inflammation through its action on NLRP6.

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.

The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2018 Feb 1;50(2):216-223. doi: 10.1093/abbs/gmx138.

DOI:10.1093/abbs/gmx138
PMID:29329362
Abstract

Visceral hypersensitivity induced by stress is quite common in irritable bowel syndrome (IBS) patients. Probiotics play an important role in reducing visceral hypersensitivity in IBS patients. However, the mechanism has not been clearly elucidated. In this study, we investigated the role of nod-like receptor pyrin domain-containing protein 6 (NLRP6) in Clostridium butyricum-regulated IBS induced by stress. Our results showed that NLRP6 was down-regulated in IBS group colon tissues. In addition, IL-18, IL-1β, myeloperoxidase (MPO), d-lactic acid (D-LA), and CD172a were up-regulated in the IBS group of colonic mucous. IL-18 and IL-1β were also increased after the NLRP6 gene was silenced. Pathological score suggested low inflammation of colonic mucous rather than terminal ileum. Water-avoidance stress (WAS) showed visceral hypersensitivity to colonic distension. However, treatment with Clostridium butyricum reversed these results, exerting a beneficial effect. In conclusion, Clostridium butyricum may exert a beneficial action on visceral hypersensitivity of IBS by inhibiting low grade inflammation of colonic mucous through its action on NLRP6.

摘要

应激引起的内脏敏感性增高在肠易激综合征(IBS)患者中很常见。益生菌在降低 IBS 患者内脏敏感性方面发挥着重要作用。然而,其机制尚未阐明。在这项研究中,我们研究了 NOD 样受体热蛋白结构域蛋白 6(NLRP6)在丁酸梭菌调节应激诱导的 IBS 中的作用。我们的结果表明,NLRP6 在 IBS 组结肠组织中下调。此外,IBS 组结肠黏膜中的 IL-18、IL-1β、髓过氧化物酶(MPO)、D-乳酸(D-LA)和 CD172a 上调。沉默 NLRP6 基因后,IL-18 和 IL-1β 也增加。病理评分提示结肠黏膜炎症程度低,而不是末端回肠。水回避应激(WAS)导致结肠扩张时内脏敏感性增加。然而,丁酸梭菌的治疗逆转了这些结果,发挥了有益的作用。总之,丁酸梭菌可能通过抑制结肠黏膜的低级别炎症来发挥对 IBS 内脏敏感性的有益作用,这是通过其对 NLRP6 的作用实现的。

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