title: Ischemic postconditioning attenuate reperfusion injury of small intestine:  impact of mitochondrial permeability transition.
abstract: BACKGROUND
  Ischemic postconditioning (IPoC) modulates the reperfusion maneuver to mitigate ischemia-reperfusion (I/R) injury. This study aims to investigate the effects and protective mechanism of IPoC on intestinal I/R injury.
  
  
  METHODS
  Intestinal I/R was induced by occluding the superior mesenteric artery for 30 min followed by reperfusion for 60 min on male Wistar rats. IPoC was elicited by three cycles of 30-sec reperfusion and reocclusion of superior mesenteric artery at the initiation of reperfusion. Carboxyatractyloside (CATR), a mitochondrial permeability transition pore (mPTP) opener, and N-methyl-4-isoleucine cyclosporine (NIM811), an mPTP inhibitor, were administered separately in selected groups. The serum and intestinal sections were collected for analysis.
  
  
  RESULTS
  IPoC and the administration of NIM811 significantly diminished the expression of intestinal-type fatty acid-binding protein and lactate dehydrogenase (3427±236.8 U/L for I/R, 1190.5±36.7 U/L for IPoC, 1399.3±295.6 U/L for I/R+NIM811, and 2002±370.9 IU/L for IPoC+CATR) in portal blood, the release of cytosolic cytochrome c, and the cleaved caspase 9 expression in intestinal mucosa after intestinal I/R injury (P<0.05). Histopathologically, IPoC and NIM811 mitigated mucosal damage after I/R as well (Chiu's score, 3.8±0.4 for I/R, 0.2±0.2 for IPoC, 0.4±0.2 for I/R+NIM811, and 4.2±0.2 for IPoC+CATR; apoptotic index, 59.5%±4.6% for I/R, 15.7%±15.7% for I/R+IPoC, 3.5%±3.5% for I/R+NIM811, and 67.1%±9.3% in IPoC+CATR). CATR negated the protection conferred by IPoC.
  
  
  CONCLUSIONS
  IPoC and NIM811 attenuate intestinal I/R injury. The addition of CATR negated the effects of IPoC, indicating that the protective mechanism of IPoC was associated with the modulation of mPTP opening.
authors: Department of Anatomy and Cell Biology, Medical College, National Taiwan University, Taipei, Taiwan.
authors: Ching-Hsueh
authors: CH
authors: Cheng
authors: Han-Chen
authors: HC
authors: Lin
authors: I-Rue
authors: IR
authors: Lai
authors: Hong-Shiee
authors: HS
authors: Lai
mesh_terms: D000818:Animals; D017209:Apoptosis; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D057775:Ischemic Postconditioning / Q000379:methods*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008026:Ligation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017538:Mesenteric Artery, Superior / Q000601:surgery; D008641:Mesenteric Vascular Occlusion / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: C493407:Fabp2 protein, rat; D050556:Fatty Acid-Binding Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D001278:Atractyloside; D008315:Malondialdehyde; D016572:Cyclosporine; D045304:Cytochromes c; C090438:(melle-4)cyclosporin; D007770:L-Lactate Dehydrogenase; C505410:Casp3 protein, rat; D053148:Caspase 3; C003853:carboxyatractyloside