title: Restraint stress aggravates rat kidney injury caused by a crush injury through endoplasmic reticulum stress.
abstract: BACKGROUND
  The present study aimed to determine whether restraint stress aggravates kidney injury caused by a crush injury through endoplasmic reticulum stress (ERS).
  
  
  METHODS
  In this study, Sprague-Dawley rat restraint stress, crush injury, and stressful injury models consisting of restraint stress and crush injury were established. An ERS inhibitor, Salubrinal (Sal), was administered intraperitoneally 30 minutes before induction of daily injury in the stressful injury group. At the end of the experimental procedures, plasma levels of noradrenaline and adrenaline, creatine phosphokinase, creatinine, and blood urea nitrogen were measured. Kidneys were harvested, and paraffin-embedded sections of kidney tissues were processed for hematoxylin-eosin staining and TUNEL assay to verify pathologic changes. Western blot was used to determine the protein levels of glucose-regulated protein 78, CCAAT/enhancer-binding protein-homologous protein, caspase 12, caspase 3, and MCP-1 in kidney specimens.
  
  
  RESULTS
  Compared with crush injury, the most significant changes in kidney injury occurred in the stressful injury group, which was inhibited by Sal. The results suggested that restraint stress aggravates kidney injury caused by a crush injury, and the mechanism might involve ERS. Further study showed that double attacks induced a significant increase in the levels of glucose-regulated protein 78, CCAAT/enhancer-binding protein-homologous protein, caspase 12, and caspase 3, which was inhibited by Sal. The same changes were observed using the TUNEL assay. Double attacks also induced an increased expression of the proinflammatory cytokine, MCP-1, which was inhibited by Sal.
  
  
  CONCLUSIONS
  Apoptosis and inflammation induced by ERS are important mechanisms by which restraint stress aggravates kidney injury caused by a crush injury.
authors.affiliation: From the Hebei Key Laboratory of Forensic Medicine (J.G., X.J.Z., C.L.M., Y.M.L., G.Z.Z., R.F.M., B.C.), Department of Forensic Medicine, and Clinical Diagnostics Department of Clinical Diagnostics (Y.Z.), Hebei Medical University, Shijiazhuang, Hebei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Geng
authors.forename: Xiao Jing
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Chun Ling
authors.initials: CL
authors.lastname: Ma
authors.forename: Ying Min
authors.initials: YM
authors.lastname: Li
authors.forename: Guo Zhong
authors.initials: GZ
authors.lastname: Zhang
authors.forename: Ru Fei
authors.initials: RF
authors.lastname: Ma
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Cong
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D003404:Creatinine / Q000378:metabolism; D003444:Crush Syndrome / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D016207:Cytokines; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP; D003404:Creatinine