The role of PI3K/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion

Abstract

Purpose To investigate the role of PI3k/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion(I/R). Methods Male Sprague-Dawley rats were subjected to 45 min of ischemia by occluding the superior mesenteric artery and to 2h of reperfusion to establish the model of I/R. Twenty four rats were randomly divided into four groups: Sham, intestinal I/R (II/R), propofol (P), wortmannin (W). In groups P, W, propofol was injected intravenously and continuously at the onset of reperfusion via infusion pump. PI3K inhibitor (wortmannin) was administered intravenously in group W 25 min before ischemia. Intestinal tissues and lung tissues were obtained for determination of histologic injury, wet/dry weight ratio, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities. Meanwhile, the expressions of caspase-3 and phosphorylated Akt (p-Akt) in intestines and lungs were detected by western blot. Results Propofol treatment alleviated intestinal and lung morphological changes which were observed in II/R group , Moreover, wet/dry weight ratio, the MDA level, MPO activity and expression of caspase-3 were significantly decreased whereas the SOD activity and p-Akt expression were significantly increased. Notably, the protections were significantly reversed by pretreatment of wortmannin. Conclusion: PI3K/Akt pathway activation play a critical role in the protective effects of propofol on intestinal and lung injury induced by ischemia/reperfusion.

The α2AR/Caveolin‐1/p38MAPK/NF‐κB axis explains dexmedetomidine protection against lung injury following intestinal ischaemia‐reperfusion

“…Lung injury is one of the common organs involved in intestinal I/R injury. In the worst case, intestinal I/R injury can even cause a life‐threatening respiratory distress syndrome 17 . Although a large number of studies have been carried out on lung injury caused by intestinal I/R in recent years, its exact pathogenesis has not been fully elucidated, and there is still a lack of effective prevention and treatment measures.…”

“…The five‐point Chiu score was used to evaluate the degree of the intestinal injury according to the changes of intestinal mucosal villi and glands 17 . The degrees of injury were Grade 0: normal mucosal villi; grade 1: development of a subepithelial space, often accompanied with capillary congestion; grade 2: prolongation of subepithelial space and moderate elevation of lamina propria epithelium; grade 3: a large number of epithelial cells rising along the side of the villus, possibly with a small amount of exfoliation; grade 4: lamina propria villi shedding, telangiectasia, lamina propria cells increase; grade 5: degradation and disintegration of the lamina propria, haemorrhage, and ulceration.…”

MicroRNA-221/222 Mediates ADSC-Exosome-Induced Cardioprotection Against Ischemia/Reperfusion by Targeting PUMA and ETS-1

“…Considering the involvement of ADSC-Exo in the reduction of I/R-induced apoptosis and hypertrophy, it is of great significance to regulate these signals. The AKT signaling pathway plays an essential role against I/R injury by regulating proapoptotic signals, inflammation and ROS ( Li Q. et al, 2019 ). Oxidative stress-induced cell apoptosis is due to AKT dysfunction and NFκB upregulation ( Wang et al, 2019 ).…”

Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

“…In recent years, Propofol (2,6-di-isopropyl phenol), an intravenous anesthetic, has been found to exert protective effects on lung injury induced by intestinal I/R (Li et al 2019). Furthermore, Propofol could lessen acute lung injury induced by renal I/R involved with autophagy (Liu et al 2020).…”