Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Bioengineered. 2022 Mar;13(3):5005-5020. doi: 10.1080/21655979.2022.2038450.
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.
在缺血再灌注损伤过程中，肠缺血和炎症交织在一起，导致组织损伤或坏死。然而，再灌注后产生的氧自由基和炎症介质再次引起组织损伤，导致严重的肠道上皮屏障功能障碍。本研究旨在确定生长抑素对肠缺血再灌注损伤期间肠道上皮屏障功能的保护作用，并探讨其机制。通过建立大鼠肠缺血再灌注模型，用生长抑素预处理大鼠，然后检测肠组织的组织病理学变化、肠道通透性和紧密连接蛋白的表达，在体内测量生长抑素对肠道上皮屏障的保护作用。在体外使用干扰素 γ (IFN-γ) 处理 Caco-2 细胞来确定机制。结果表明，生长抑素可以改善缺血再灌注引起的肠道上皮屏障功能障碍，并保护 Caco-2 细胞免受 IFN-γ引起的紧密连接蛋白表达降低和单层细胞通透性增加的影响。生长抑素在缺血再灌注大鼠和 IFN-γ处理的 Caco-2 细胞中均上调 Tollip 的表达，同时抑制 TLR2/MyD88/NF-κB 信号的激活。Tollip 抑制逆转了生长抑素对肠道上皮屏障的保护作用。总之，生长抑素通过上调 Tollip 抑制 TLR2/MyD88/NF-κB 信号的激活，减轻缺血再灌注引起的肠道上皮屏障损伤。
