title: Protective effect of pioglitazone on sepsis-induced intestinal injury in a rodent model.
abstract: BACKGROUND
  Pathogenesis and treatment of inflammatory gut barrier failure is an important problem in critical care. In this study, we examined the role of pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, in gut barrier failure during experimental peritonitis in rats.
  
  
  METHODS
  Male rats were randomly divided into three groups as follows: sham, sepsis, and sepsis + pioglitazone. Sepsis was achieved by means of the cecal ligation and puncture (CLP). Pioglitazone was administered intraperitoneally (10 mg/kg/d) for 7 d before the experiment. Animals were killed at 24 h or followed 72 h for survival. The tissue level of tumor necrosis factor-α, interleukin-6, superoxide dismutase, malondialdehyde, and myeloperoxidase was measured. Intestinal mucosa injury was assessed histologically. The plasma fluorescein isothiocyanate-dextran, D-lactic acid, and intestinal diamine oxidase were determined to evaluate the permeability and integrity of intestinal mucosal epithelium. Vena cava blood and tissue samples were used to monitor bacterial translocation.
  
  
  RESULTS
  Intestinal inflammation, oxidize stress, neutrophil infiltration, morphology injury, and impaired permeability of the small intestine in the CLP group were found more severe than those in the sham group. Application of pioglitazone not only minimized all the indicators of intestinal injury and barrier failure but also improved the survival of septic rats induced by CLP.
  
  
  CONCLUSIONS
  Our novel findings suggest that pioglitazone could protect against intestinal injury and maintain intestinal barrier integrity and might be a useful strategy to ameliorate intestinal failure in polymicrobial sepsis.
authors.affiliation: Department of Emergency and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; Translational Medicine Center of Sepsis, Department of Pathophysiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: Laboratory of Shock, Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Emergency and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Emergency and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; Translational Medicine Center of Sepsis, Department of Pathophysiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Translational Medicine Center of Sepsis, Department of Pathophysiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; Laboratory of Shock, Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Emergency and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; Translational Medicine Center of Sepsis, Department of Pathophysiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. Electronic address: xyyms2004@163.com.
authors.forename: Mingshi
authors.initials: M
authors.lastname: Yang
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists*; D010539:Permeability; D009195:Peroxidase / Q000032:analysis; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015850:Interleukin-6; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D006631:Amine Oxidase (Copper-Containing); D000077205:Pioglitazone
keywords: Cecal ligation and puncture; Intestinal injury; Pioglitazone; Sepsis