嗜热栖热菌 HB27 来源的锰超氧化物歧化酶抑制炎症反应并缓解实验性结肠炎。

A Manganese-Superoxide Dismutase From Thermus thermophilus HB27 Suppresses Inflammatory Responses and Alleviates Experimentally Induced Colitis.

机构信息

MOE Key Laboratory of Model Animal for Disease Study and State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Nanjing University, Nanjing, China.

Institute of Molecular Enzymology, Medical College of Soochow University, Jiangsu, China.

出版信息

Inflamm Bowel Dis. 2019 Sep 18;25(10):1644-1655. doi: 10.1093/ibd/izz097.

DOI:10.1093/ibd/izz097

PMID:31067299

Abstract

BACKGROUND

Superoxide dismutase (SOD) is an attractive therapeutic agent to ameliorate oxidative stress that is critical for the initiation and progression of inflammatory bowel disease (IBD). However, the short life of SOD limits its clinical application. In this study, we aim to examine the therapeutic effects of a hyperthermostable SOD from the Thermus thermophilus HB27 (TtSOD) for treatment of experimentally induced IBD.

METHODS

A recombinant TtSOD was expressed and purified from Escherichia coli, and its therapeutic effects were examined in 2 experimental IBD animal models.

RESULTS

In IBD induced by 2,4,6-trinitrobenzenesulfonic acid in zebrafish, TtSOD treatment decreased intestinal enlargement and attenuated neutrophil infiltration, resulting in alleviation of enterocolitis. In mice, SOD activity was substantially increased in the intestine after oral gavage of TtSOD, which ameliorated gut inflammation, preserved gut barrier function, and attenuated the severity of dextran sulfate sodium-induced colitis. Furthermore, TtSOD inhibited lipopolysaccharide-induced production of reactive oxygen species and inflammatory responses in mouse bone marrow-derived macrophages.

CONCLUSIONS

Our results demonstrate that TtSOD possesses therapeutic activities toward experimentally induced IBD, offering new clinical treatment options for patients with IBD.

摘要

背景

超氧化物歧化酶（SOD）是一种有吸引力的治疗剂，可以改善氧化应激，这对于炎症性肠病（IBD）的发生和发展至关重要。然而，SOD 的短寿命限制了其临床应用。在这项研究中，我们旨在研究来自 Thermus thermophilus HB27（TtSOD）的超耐热 SOD 治疗实验性诱导的 IBD 的治疗效果。

方法

从大肠杆菌中表达和纯化重组 TtSOD，并在 2 种实验性 IBD 动物模型中检查其治疗效果。

结果

在三硝基苯磺酸诱导的斑马鱼 IBD 中，TtSOD 治疗可减轻肠道肿大并减弱中性粒细胞浸润，从而减轻肠炎。在小鼠中，口服 TtSOD 后肠道中 SOD 活性显著增加，可改善肠道炎症，维持肠道屏障功能，并减轻葡聚糖硫酸钠诱导的结肠炎的严重程度。此外，TtSOD 抑制了脂多糖诱导的小鼠骨髓来源的巨噬细胞中活性氧物质和炎症反应的产生。