The role of PI3K/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion1

Acta Cir Bras. 2019 Feb 14;34(1):e20190010000005. doi: 10.1590/s0102-865020190010000005.

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.

MeSH terms

  • Anesthetics, Intravenous / pharmacology*
  • Animals
  • Disease Models, Animal
  • Lung Injury / prevention & control*
  • Male
  • Mesenteric Ischemia / drug therapy*
  • Mesenteric Ischemia / metabolism
  • Phosphatidylinositol 3-Kinases / physiology*
  • Propofol / pharmacology*
  • Proto-Oncogene Proteins c-akt / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Signal Transduction / physiology

Substances

  • Anesthetics, Intravenous
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Propofol