Xu Xin, Zhu Quanli, Li Guoliang, Ma Junjian, Pan Zhijian, Wu Wei
Department of Gastrointestinal Hepatobiliary Surgery, The Affiliated Hospital of Hangzhou Normal University, Gongshu, Hangzhou 310015, China.
Gastroenterol Res Pract. 2020 Dec 10;2020:2549486. doi: 10.1155/2020/2549486. eCollection 2020.
Somatostatin (SST) has a protective role in intestinal injury, inflammatory response, and intestinal mucosal barrier in rats with acute pancreatitis. However, its function in sepsis-induced intestinal barrier dysfunction remains largely unknown. A mouse sepsis model was constructed, and SST was injected into the tail vein. Then, hematoxylin and eosin staining (HE) was used to detect the intestinal barrier dysfunction. Enzyme-linked immunosorbent assay was used to detect the level of tumor necrosis factor - (TNF-) , interleukin- (IL-) 6, and interleukin- (IL-) 10 in the ileum. Expressions of tight junction proteins, zonula occludens- (ZO-) 1 and Claudin-1, and NF-B p65 in the ileum were detected using western blot and immunohistochemistry as needed. Furthermore, JSH-23 as an inhibitor of the NF-B pathway was injected into sepsis mice with SST or not. Mice with sepsis showed an obvious intestinal barrier dysfunction with decreasing specific somatostatin receptor subtype (SSTRs), and increasing TNF-, IL-6, and IL-10 in the ileum. SST could relieve the injury, the decrease of SSTRs, and the increase of TNF- and IL-6 induced by sepsis and also further enhanced the expression of IL-10. Further analysis showed that ZO-1 and Claudin-1 were reduced in the ileum by sepsis but enhanced by SST. NF-B p65 was promoted in the ileum by sepsis but inhibited by SST. Further experiments confirmed that NF-B inhibitor JSH-23 could repair the intestinal barrier dysfunction and enhance the protective effect of SST on the intestinal barrier. SST, with a protective effect on intestinal barrier dysfunction through suppression of NF-B, could be a potential therapeutic drug for sepsis-induced intestinal barrier dysfunction.
生长抑素（SST）对急性胰腺炎大鼠的肠道损伤、炎症反应及肠黏膜屏障具有保护作用。然而，其在脓毒症诱导的肠屏障功能障碍中的作用仍 largely 未知。构建小鼠脓毒症模型，并经尾静脉注射 SST。然后，采用苏木精-伊红染色（HE）检测肠屏障功能障碍。采用酶联免疫吸附测定法检测回肠中肿瘤坏死因子 -（TNF-）、白细胞介素-（IL-）6 和白细胞介素-（IL-）10 的水平。根据需要，使用蛋白质印迹法和免疫组织化学法检测回肠中紧密连接蛋白、闭合蛋白-（ZO-）1 和 Claudin-1 以及 NF-κB p65 的表达。此外，将作为 NF-κB 通路抑制剂的 JSH-23 注射到注射或未注射 SST 的脓毒症小鼠体内。脓毒症小鼠表现出明显的肠屏障功能障碍，特异性生长抑素受体亚型（SSTRs）减少，回肠中 TNF-、IL-6 和 IL-10 增加。SST 可减轻脓毒症诱导的损伤、SSTRs 减少以及 TNF-和 IL-6 增加，还可进一步增强 IL-10 的表达。进一步分析表明，脓毒症使回肠中的 ZO-1 和 Claudin-1 减少，但 SST 可使其增强。脓毒症使回肠中的 NF-κB p65 升高，但 SST 可抑制其升高。进一步实验证实，NF-κB 抑制剂 JSH-23 可修复肠屏障功能障碍，并增强 SST 对肠屏障的保护作用。SST 通过抑制 NF-κB 对肠屏障功能障碍具有保护作用，可能是治疗脓毒症诱导的肠屏障功能障碍的潜在药物。
