title: Hypoxia-Inducible Factor-1α Gene Expression and Apoptosis in Ischemia-Reperfusion Injury: A Rat Model of Early-Stage Pressure Ulcer.
abstract: BACKGROUND
  Pressure ulcer (PU) is a significant and complicated health problem. Although ischemia-reperfusion (I/R) injury has been identified as the primary mechanism in the early stage of pressure ulceration, the cellular and molecular events contributing to I/R injury of PU development are unclear.
  
  
  OBJECTIVE
  The aim of this study was to characterize hypoxia-inducible factor-1α (HIF-1α) expression profile and elaborate the apoptotic pathways based on an I/R injury model of PU in rats.
  
  
  METHODS
  Two related experiments were conducted. The purpose of Experiment 1 was to establish an animal model of early-stage PU (Stage I PU). Forty-eight rats were randomly divided into six groups of eight. Each group received three cycles of I/R, but with different magnitudes of pressure-which ranged from 100 to 270 mm Hg-except for Control Group A. On the basis of this established animal model, Experiment 2 focused on the I/R mechanism of early-stage PU. The 36 rats used in Experiment 2 were randomly divided into one control and two experimental groups; the experimental groups received the same magnitude of pressure (170 mm Hg), but either 3 or 5 I/R cycles. Tissue underneath the compressed region, including the skin and muscle tissue, was incised for immunohistochemistry, enzyme-linked immunosorbent assay, TdT-mediated dUTP nick-end labeling, and real-time polymerase chain reaction gene expression analysis.
  
  
  RESULTS
  HIF-1α gene expression in the compressed muscle tissue was slightly reduced in the 3 I/R group, but significantly elevated in the 5 I/R group (p < .05). The compressed tissue showed inflammation and evidence of oxidative stress reaction. ATPase activity was lower when cycles of I/R were prolonged. TdT-mediated dUTP nick-end labeling analysis showed a significant increase in the compressed muscle tissue relative to the control. Bax and Bcl-2 proteins expressed reversely.
  
  
  CONCLUSIONS
  These results suggest that mitochondria-mediated apoptotic pathways may be involved in the development of early-stage PU, and HIF-1α might play a potential role for promoting apoptosis. Inflammation, oxidative stress reaction, and energy depletion may cooperate in the process of I/R injury of early-stage PU.
authors.affiliation: Yanyan Wang, MSN, RN, is PhD student; Lihui Pu, MSN, RN, is Research Assistant; Zhi Li, MSN, RN, is Instructor; and Xiuying Hu, PhD, RN, is Professor and Dean, Nursing School, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, China. Liping Jiang, PhD, RN, is Dean, Nursing School, Wenzhou Medical University, Zhejiang, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Lihui
authors.initials: L
authors.lastname: Pu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Xiuying
authors.initials: X
authors.lastname: Hu
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001706:Biopsy; D020405:Dermis / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D003668:Pressure Ulcer / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D009195:Peroxidase; D020780:Matrix Metalloproteinase 9; D000251:Adenosine Triphosphatases