Effects of different ischemic preconditioning strategies on physiological and cellular mechanisms of intestinal ischemia/reperfusion injury: Implication from an isolated perfused rat small intestine model

Abstract

Background Intestinal ischemia/reperfusion (I/R)-injury often results in sepsis and organ failure and is of major importance in the clinic. A potential strategy to reduce I/R-injury is the application of ischemic preconditioning (IPC) during which repeated, brief episodes of I/R are applied. The aim of this study was to evaluate physiological and cellular effects of intestinal I/R-injury and to compare the influence of in-vivo IPC (iIPC) with ex-vivo IPC (eIPC), in which blood derived factors and nerval regulations are excluded. Methods Using an established perfused rat intestine model, effects of iIPC and eIPC on physiological as well as cellular mechanisms of I/R-injury (60 min hypoxia, 30 min reperfusion) were investigated. iIPC was applied by three reversible occlusions of the mesenteric artery in-vivo for 5 min followed by 5 min of reperfusion before isolating the small intestine, eIPC was induced by stopping the vascular perfusion ex-vivo 3 times for 5 min followed by 5 min of reperfusion after isolation of the intestine. Study groups (each N = 8–9 animals) were: iIPC, eIPC, I/R (iIPC group), I/R (eIPC group), iIPC+I/R, eIPC+I/R, no intervention/control (iIPC group), no intervention/control (eIPC group). Tissue morphology/damage, metabolic functions, fluid shifts and barrier permeability were evaluated. Cellular mechanisms were investigated using signaling arrays. Results I/R-injury decreased intestinal galactose uptake (iIPC group: p<0.001), increased vascular perfusion pressure (iIPC group: p<0.001; eIPC group: p<0.01) and attenuated venous flow (iIPC group: p<0.05) while lactate-to-pyruvate ratio (iIPC group, eIPC group: p<0.001), luminal flow (iIPC group: p<0.001; eIPC group: p<0.05), goblet cell ratio (iIPC group, eIPC group: p<0.001) and apoptosis (iIPC group, eIPC group: p<0.05) were all increased. Application of iIPC prior to I/R increased vascular galactose uptake (P<0.05) while eIPC had no significant impact on parameters of I/R-injury. On cellular level, I/R-injury resulted in a reduction of the phosphorylation of several MAPK signaling molecules. Application of iIPC prior to I/R increased phosphorylation of JNK2 and p38δ while eIPC enhanced CREB and GSK-3α/β phosphorylation. Conclusion Intestinal I/R-injury is associated with major physiological and cellular changes. However, the overall influence of the two different IPC strategies on the acute phase of intestinal I/R-injury is rather limited.

A Novel Polysaccharide From Chuanminshen violaceum and Its Protective Effect Against Myocardial Injury

“…Chuanminshen violaceumis polysaccharide sample (20 mg) was dissolved in 0.5 ml D 2 O for nuclear magnetic resonance (NMR) analysis. 1 H, 13 C, 1 H-1 H, Correlation Spectroscopy (COSY), Heteronuclear Singular Quantum Correlation (HSQC), and Heteronuclear Multiple Bond Correlation (HMBC) spectra were recorded on a Bruker Ascend 600 MHz Spectrometer.…”

“…The 13 C NMR spectrum showed that the corresponding anomeric carbons are at δ 98.55, 99.35, 99.49, 99.71, 99.58, and 99.4 ppm (Figure 2B). According to the results of methylation and NMR spectra, proton and carbon signals were confirmed at δ 61.17/3.74, 3.66; δ 61.09/3.74, 3.64; and δ 60.41-60.45/3.76-3.80.…”

“…Therefore, inhibition of oxidative stress and inflammatory response is widely accepted as the optimum therapeutic strategy for I/R injury ( 8 ). However accumulated clinical feedback reveals that serious side effects remain a vital challenge in dealing with oxidative damage, such as acute kidney injury ( 9 ), arrhythmia ( 10 , 11 ), hypertension ( 12 ), sepsis ( 13 ), and bowel infarct ( 14 ). Therefore, there is an increasing demand for potential natural products with lower toxicity and fewer side effects.…”

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 ).…”

Reversible 'unstable' abdominal angina caused by ruptured plaque of the superior mesenteric artery: clinical and radiological correlations

“…Atherosclerosis has been implicated in the aetiology of the overwhelming majority of cases of CMI, characterized by chronic abdominal visceral pain aggravated by meals and associated with anorexia and weight loss [ 1 ] . In most cases, CMI reflects multi-vessel chronic stable mesenteric disease, with substantial mesenteric ischaemia beyond the mitigating capacity of hypoxia adaptation [ 2 , 3 ] and the formation of collaterals [ 4 , 5 ] . By contrast, AMI reflects an acute arterial occlusion, manifested by an abrupt and catastrophic presentation.…”