title: Role of autophagy and apoptosis in wound tissue of deep second-degree burn in rats.
abstract: OBJECTIVE
  The pathogenesis of burn wound progression is poorly understood. Contributing factors include continuous loss of blood perfusion, excessive inflammation, and elevated apoptosis levels in wound tissue. Macroautophagy (here referred to simply as "autophagy") is associated with many chronic diseases. The authors hypothesized that autophagy is involved in burn wound progression in a rat model of deep second-degree burn.
  
  
  METHODS
  Deep second-degree burns were modeled using a brass rod heated to 100°C applied for 6 seconds to the back skin of Wistar rats. Full-thickness biopsies were obtained from burned and nonburned controls at several times postburn. Western blotting and immunohistochemical (IHC) staining determined expression of the autophagy markers Light Chain 3 (LC3) and beclin-1. Apoptosis was determined by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and laser Doppler flowmetry (LDF)-measured tissue perfusion. Myeloperoxidase (MPO) activity assay measured inflammation. Hematoxylin and eosin (H&E) and Masson's trichrome staining-determined pathology and wound depth.
  
  
  RESULTS
  The LC3 and beclin-1 protein level in burn wounds decreased to one-fourth of normal levels (p<0.01) over 24 hours and then began to increase but still did not reach their normal level. TUNEL-positive cells in burn wounds were 3.7-fold (p<0.01) elevated over 48 hours and then decreased slightly, yet still remained higher than in normal skin. The burn wound progressed in depth over 72 hours. In addition, significant decrease in LDF values and upregulation of MPO activity were observed. Enhanced LC3-positive cells were observed in the deep dermal layer of burn wounds as shown by IHC staining.
  
  
  CONCLUSIONS
  A reduction in autophagy and blood flow and an increase in apoptosis and inflammation were observed in burn wounds early during the course of burn injury progression. This suggests that autophagy, complemented by apoptosis, play important roles in burn progression. Enhanced autophagy in the deep dermis may be a prosurvival mechanism against ischemia and inflammation after burn injury.
authors.affiliation: The Department of Burn and Plastic Surgery, Burn Institute First Affiliated Hospital of General Hospital of PLA, Beijing, China.
authors.forename: Mengjing
authors.initials: M
authors.lastname: Xiao
authors.forename: Ligen
authors.initials: L
authors.lastname: Li
authors.forename: Chenxi
authors.initials: C
authors.lastname: Li
authors.forename: Peirong
authors.initials: P
authors.lastname: Zhang
authors.forename: Quan
authors.initials: Q
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002056:Burns / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers
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