Rapamycin alleviated pulmonary injury induced by fat embolism syndrome in rats

Biochem Biophys Res Commun. 2018 Nov 30;506(3):504-509. doi: 10.1016/j.bbrc.2018.10.105. Epub 2018 Oct 22.

Abstract

Fat embolism syndrome (FES) is a serious complication after trauma, surgery and fat emulsion input and can lead to serious pulmonary injury. Autophagy controls the cell survival and homeostasis by removing the mis-folded proteins and damaged organelles as well as intracellular pathogens through a lysosomal degradation pathway. Increasing research documented that autophagy was wildly involved in variety of human diseases and had huge therapeutic potential. However, the role and mechanism of autophagy in FES remains largely unknown. The rat model of FES was established by tail vein injection with fat and was assessed by Wet-to-Dry (W/D) ratio analysis, hematoxylin-eosin (HE) analysis, staining Oil red staining analysis and qPCR analysis. Western blots were employed to detect the expression of autophagy markers. The changes of pulmonary injury were observed after premedication of rapamycin (an autophagy activator). The alveolar structural damage, red free fat substances in the blood vessels of lung, increased the lung ratio, and the up-regulated MPO expression and activity were showed in the FES models. The expressions of autophagy markers were decreased and meanwhile, apoptosis markers were increased in the FES model. Rapamycin restored the expression of autophagy markers and inhibited the apoptosis and further, resulting in the improvement of the pulmonary injury. Thus, our study demonstrated that autophagy was inhibited and apoptosis was promoted in FES and further Rapamycin alleviated the pulmonary damage in FES via restoring the autophagy and inhibiting the apoptosis.

Keywords: Apoptosis; Autophagy; Fat embolism syndrome; Pulmonary injury; Rapamycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / transplantation
  • Allografts / transplantation
  • Animals
  • Apoptosis
  • Autophagy
  • Disease Models, Animal
  • Embolism, Fat / complications*
  • Lung Injury / drug therapy*
  • Lung Injury / etiology*
  • Male
  • Rats, Wistar
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use*

Substances

  • Sirolimus