Ischemic postconditioning attenuate reperfusion injury of small intestine: Impact of mitochondrial permeability transition
Journal
Transplantation
Journal Volume
95
Journal Issue
4
Pages
559-565
Date Issued
2013
Author(s)
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.
SDGs
Type
journal article