Role of autophagy and its molecular mechanisms in mice intestinal tract after severe burn

Authors:
  • WQWei Qiu
    Wei Qiu
  • PJPeiS Jin
    PeiS Jin
  • PWPeng Wang
    Peng Wang
  • YSYong Sun
    Yong Sun
Publisher website
Google Scholar
Abstract
Severe burn can lead to hypoxia/ischemia of intestinal mucosa. Autophagy is the process of intracellular degradation, which is essential for cell survival under stresses such as hypoxia/ischemia and nutrient deprivation. The present study was designed to investigate whether there were changes in intestinal autophagy after severe burn in mice and further to explore the effect and molecular mechanisms of autophagy on intestinal injury. This study includes three experiments. Kunming-species mice were subjected to 30% total body surface area 3rd degree burn. First, we determined protein of LC3 (light chain 3), beclin-1 and cleaved-caspase3 by Western blotting and Immunohistochemical (paraffin) staining to investigate whether there were changes in intestinal autophagy after severe burn in mice. Following, changes of the status of enteric damage post-burn were measured by observing intestinal mucosa morphology under a magnifier, Hematoxylin and eosin(H&E) staining, ELISA, Western blotting under the condition that the intestinal autophagy was respectively activated by Rapamycin and inhibited by 3-Methyladenine (3-MA). Finally, protein of the AMPK (AMP-activated protein kinase)/mTOR (Mammalian target of rapamycin) pathway, LC3-II and beclin-1 were assayed, and mice were treated with compound C before burn. The protein of LC3 and beclin-1 were observed at 1h post-burn and increased to peak-point at 24h, reaching the normal level at 96h. The cleaved caspase-3 expression increased at 1h post-burn, but the peak-point occurred at 12h and had dropped to normal level at 72h. In addition, rapamycin enhanced intestinal autophagy and alleviated burn-induced gut damage, while 3-Methyladenine showed the against behavior. The AMPK/mTOR pathway which was inhibited decreased the expression of phosphorylated AMPK, LC3-II, and beclin-1, increasing the expression of phosphorylated mTOR. Intestinal autophagy is activated and response to intestinal apoptosis after serious burn, which alleviated burn-induced intestinal injury. The AMPK/mTOR pathway may involve in activation of burn-induced autophagy. Therapeutic/care management, levels of evidence are not applicable to some studies, such as in vitro work, animal models, cadaver studies.

This publication has 46 references indexed in Scilit: