Remote ischemic post‑conditioning alleviates ischemia/reperfusion‑induced intestinal injury via the ERK signaling pathway‑mediated RAGE/HMGB axis

Abstract

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.

A novel stroke rehabilitation strategy and underlying stress granule regulations through inhibition of NLRP3 inflammasome activation

“…It is well established that RIC is associated with reduced levels of the pro‐inflammatory cytokines following cerebral infarction 37,49,50 . In intestinal I/R injury mouse models, RIC was demonstrated to suppress the NF‐κB/NLRP3 inflammatory pathways via the ERK pathway 51 . A link between early RIC after ischemic stroke with NLRP3 inflammasome was suggested in our current study, and furthermore, investigations are warranted to examine a cause‐and‐effect relationship.…”

The effects of different stress on intestinal mucosal barrier and intestinal microecology were discussed based on three typical animal models

“…At present, more and more enteric bacteria have been found to have the potential to treat intestinal and extraintestinal organ damage caused by intestinal IIRI. But since the pathogenesis of IIRI is not yet fully understood, clinical treatment or prevention is mostly aimed at alleviating acute injury by simulating several links in the process of IIRI, such as ischemic preconditioning and ischemic postconditioning ( Wong et al., 2021 ; Mi et al., 2021 ).…”

Prmt6-Foxo3a Attenuates Apoptosis by Upregulating Parkin Expression in Intestinal Ischemia-Reperfusion Injury

“…For clinical surgeons, IIRI has been a persistent issue for a significant period (3). Because of intestine's high energy requirements and continuous exposure to a varying blood supply, surgery patients are prone to IIRI, which can lead to intestinal anastomotic leakage, prolonged hospitalization, and increased morbidity and mortality (4,5). On the other hand, the pathophysiology of IIRI is complex and involves a variety of interconnected mechanisms, including oxidative stress, inflammation, necrosis, and apoptotic cell death (6,7).…”