Intestinal ischemia reperfusion (I/R) injury is a tissue and organ injury that frequently occurs during surgery and significantly contributes to the pathological processes of severe infection, injury, shock, cardiopulmonary insufficiency and other diseases. However, the mechanism of intestinal I/R injury remains to be elucidated. A mouse model of intestinal I/R injury was successfully established and the model mice were treated with remote ischemic post‑conditioning (RIPOC) and/or an ERK inhibitor (CC‑90003), respectively. Histopathological changes of the intestinal mucosa were determined by hematoxylin and eosin staining. In addition, the levels of high‑mobility group box 1 (HMGB1) and receptor for advanced glycation end products (RAGE) expression were confirmed by reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry assays. The levels of antioxidants, oxidative stress markers (8‑OHdG) and interleukin 1 family members were evaluated by ELISA assays and the levels of NF‑κB pathway proteins were analyzed by western blotting. The data demonstrated that RIPOC could attenuate the histopathological features of intestinal mucosa in the intestinal I/R‑injury mouse models via the ERK pathway. It was also revealed that HMGB1 and RAGE expression in the mouse models could be markedly reduced by RIPOC (P<0.05) and that these reductions were associated with inhibition of the ERK pathway. Furthermore, it was demonstrated that RIPOC produced significant antioxidant and anti‑inflammatory effects following an intestinal I/R injury and that these effects were mediated via the ERK pathway (P<0.05). In addition, RIPOC was demonstrated to suppress the NF‑κB (p65)/NLR family pyrin domain containing 3 (NLRP3) inflammatory pathways in the intestinal I/R injury mouse models via the ERK pathway. The findings of the present study demonstrated that RIPOC helped to protect mice with an intestinal I/R injury by downregulating the ERK pathway.

中文翻译：

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远程缺血后处理通过 ERK 信号通路介导的 RAGE/HMGB 轴减轻缺血/再灌注诱导的肠损伤。

肠缺血再灌注(I/R)损伤是一种在手术过程中频繁发生的组织器官损伤，对严重感染、损伤、休克、心肺功能不全等疾病的病理过程有重要影响。然而，肠道 I/R 损伤的机制仍有待阐明。成功建立了小鼠肠道 I/R 损伤模型，并分别对模型小鼠进行了远程缺血后处理 (RIPOC) 和/或 ERK 抑制剂 (CC-90003) 治疗。通过苏木精和伊红染色确定肠粘膜的组织病理学变化。此外，通过逆转录定量聚合酶链反应证实了高迁移率组框 1 (HMGB1) 和晚期糖基化终产物受体 (RAGE) 表达的水平，蛋白质印迹和免疫组织化学测定。通过 ELISA 测定评估抗氧化剂、氧化应激标志物 (8-OHdG) 和白细胞介素 1 家族成员的水平，并通过蛋白质印迹分析 NF-κB 通路蛋白的水平。数据表明，RIPOC 可以通过 ERK 通路减弱肠道 I/R 损伤小鼠模型中肠黏膜的组织病理学特征。还表明，小鼠模型中 HMGB1 和 RAGE 的表达可以通过 RIPOC 显着降低（P<0.05），并且这些降低与 ERK 通路的抑制有关。此外，研究表明 RIPOC 在肠道 I/R 损伤后产生显着的抗氧化和抗炎作用，并且这些作用是通过 ERK 通路介导的（P<0.05）。此外，RIPOC 被证明可通过 ERK 通路抑制肠道 I/R 损伤小鼠模型中含有 3 个 (NLRP3) 炎症通路的 NF-κB (p65)/NLR 家族 pyrin 结构域。本研究的结果表明，RIPOC 通过下调 ERK 通路有助于保护患有肠道 I/R 损伤的小鼠。