Department of Gastrointestinal Surgery, Tai'an City Central Hospital, Tai'an, Shandong 271000, P.R. China.
Mol Med Rep. 2021 Nov;24(5). doi: 10.3892/mmr.2021.12413. Epub 2021 Sep 7.
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.
肠缺血再灌注（I/R）损伤是一种组织和器官损伤，在手术中经常发生，并显著促进严重感染、损伤、休克、心肺功能不全等疾病的病理过程。然而，肠 I/R 损伤的机制仍有待阐明。成功建立了肠 I/R 损伤的小鼠模型，并分别用远程缺血后处理（RIPOC）和/或 ERK 抑制剂（CC-90003）处理模型小鼠。通过苏木精和伊红染色法测定肠黏膜的组织病理学变化。此外，通过逆转录-定量聚合酶链反应、western blot 及免疫组织化学法检测高迁移率族蛋白 1（HMGB1）和晚期糖基化终产物受体（RAGE）的表达水平。通过 ELISA 法评估抗氧化剂、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 western blot 法分析 NF-κB 通路蛋白的水平。结果表明，RIPOC 可通过 ERK 通路减轻肠 I/R 损伤小鼠模型的肠黏膜组织学特征。还揭示了 RIPOC 可显著降低小鼠模型中 HMGB1 和 RAGE 的表达（P<0.05），且这种降低与 ERK 通路的抑制有关。此外，研究还表明，RIPOC 在肠 I/R 损伤后产生显著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 还通过 ERK 通路抑制肠 I/R 损伤小鼠模型中的 NF-κB（p65）/NLR 家族含吡喃结构域蛋白 3（NLRP3）炎症通路。本研究的结果表明，RIPOC 通过下调 ERK 通路有助于保护肠 I/R 损伤的小鼠。
