title: A quantitative study of p38 mitogen-activated protein kinase on renal dysfunction after hemorrhagic shock in rats.
abstract: BACKGROUND
  The severity of renal dysfunction correlates with fatal outcome after hemorrhagic shock. However, the precise mechanism for increasing renal dysfunction in response to the degree and the progression of hemorrhagic shock has not been clearly demonstrated. In this study, we examined the role of p38 mitogen-activated protein kinase (MAPK) activation on the progression of renal dysfunction by studying the differential severity of bleeding.
  
  
  METHODS
  Hemorrhagic shock was studied by quantitatively grading four groups of hemorrhaging rats: not hemorrhaged (Sham group); hemorrhaged up to 16.7% of their total body blood volume (16.7% group); hemorrhaged up to 25% (25% group); and hemorrhaged up to 33% (33% group). Mean arterial blood pressure and renal blood flow were recorded up to 5 hours after the bleeding. Kidneys were excised for assays of p38 MAPK and mRNA of the proinflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β, and for histopathological study. The levels the cytokines and creatinine were measured in the renal venous blood.
  
  
  RESULTS
  As the amount of bleeding increased, the initial activation of p38 MAPK and the expression of renal cytokines were progressively enhanced. The severity of renal dysfunction, manifested by serum creatinine concentration, histologic damage score, and neutrophil accumulation in the kidney, was well correlated with the degree of initial p38 MAPK activation.
  
  
  CONCLUSIONS
  The increase of initial p38 MAPK activation after hemorrhagic shock quantitatively enhanced the ensuing renal dysfunction in response to the degree and the progression of hemorrhagic shock.
authors.affiliation: Department of Forensic Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. h-sato@med.uoeh-u.ac.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sato
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kasai
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003404:Creatinine / Q000097:blood; D004789:Enzyme Activation; D053583:Interleukin-1beta / Q000032:analysis / Q000502:physiology; D007668:Kidney / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D012771:Shock, Hemorrhagic / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D003404:Creatinine; D048051:p38 Mitogen-Activated Protein Kinases