Somatostatin attenuates intestinal epithelial barrier injury during acute intestinal ischemia–reperfusion through Tollip/Myeloiddifferentiationfactor 88/Nuclear factor kappa-B signaling

In the process of ischemia–reperfusion injury, intestinal ischemia and inflammation interweave, leading to tissue damage or necrosis. However, oxygen radicals and inflammatory mediators produced after reperfusion cause tissue damage again, resulting in severe intestinal epithelial barrier dysfunction. The aim of this study was to determine the protective effect of somatostatin on intestinal epithelial barrier function during intestinal ischemia–reperfusion injury and explore its mechanism. By establishing a rat intestinal ischemia–reperfusion model, pretreating the rats with somatostatin, and then detecting the histopathological changes, intestinal permeability and expression of tight junction proteins in intestinal tissues, the protective effect of somatostatin on the intestinal epithelial barrier was measured in vivo. The mechanism was determined in interferon γ (IFN-γ)-treated Caco-2 cells in vitro. The results showed that somatostatin could ameliorate ischemia–reperfusion-induced intestinal epithelial barrier dysfunction and protect Caco-2 cells against IFN-γ-induced decreases in tight junction protein expression and increases in monolayer cell permeability. The expression of Tollip was upregulated by somatostatin both in ischemia–reperfusion rats and IFN-γ-treated Caco-2 cells, while the activation of TLR2/MyD88/NF-κB signaling was inhibited by somatostatin. Tollip inhibition reversed the protective effect of somatostatin on the intestinal epithelial barrier. In conclusion, somatostatin could attenuate ischemia–reperfusion-induced intestinal epithelial barrier injury by inhibiting the activation of TLR2/MyD88/NF-κB signaling through upregulation of Tollip.

在缺血-再灌注损伤进程中，肠缺血与炎症相互交织，引发组织损伤乃至坏死。而再灌注后产生的氧自由基与炎症介质会再次造成组织损伤，进而引发严重的肠上皮屏障功能障碍。本研究旨在明确生长抑素（somatostatin）在肠缺血-再灌注损伤过程中对肠上皮屏障功能的保护作用，并探究其潜在机制。本研究通过构建大鼠肠缺血-再灌注模型，给予生长抑素预处理，随后检测肠组织的病理组织学变化、肠通透性及紧密连接蛋白表达水平，在体内层面评估生长抑素对肠上皮屏障的保护作用；其具体机制则通过体外经γ干扰素（interferon γ, IFN-γ）处理的Caco-2细胞模型进行验证。结果显示，生长抑素可改善缺血-再灌注诱导的肠上皮屏障功能障碍，同时能够拮抗IFN-γ诱导的Caco-2细胞紧密连接蛋白表达下调及单层细胞通透性升高。在缺血-再灌注损伤大鼠模型及IFN-γ处理的Caco-2细胞中，生长抑素均可上调Tollip的表达，同时抑制TLR2/MyD88/NF-κB信号通路的激活。抑制Tollip的表达则会逆转生长抑素对肠上皮屏障的保护作用。综上，生长抑素可通过上调Tollip的表达，抑制TLR2/MyD88/NF-κB信号通路的激活，从而减轻缺血-再灌注诱导的肠上皮屏障损伤。