ABSTRACT
Adrenomedullin (AM) is a peptide proven to increase cellular tolerance to hypoxia and oxidative stresss and contribute angiogenesis. Despite its known therapeutic effects on myocardial, renal or spinal ischemic reperfusion injuries, its local and systemic effects on intestinal ischemic reperfusion injury still remain unknown. This study aims to demonstrate the local and systemic effects of AM on Intestinal Ischemic Reperfusion Injury (I-IRI) demonstrated in rats. Thirty male rats were randomly allocated to five groups: Control, Adrenomedullin (AM), Intestinal Ischemic Reperfusion Injury (I-IRI), Adrenomedullin and Intestinal Ischemic Reperfusion Injury (AM+I-IRI), and Intestinal Ischemic Reperfusion Injury and Adrenomedullin (I-IRI+AM). Blood and tissue samples were obtained for biochemical and histopathological evaluation. The results were expressed as mean±SEM and, P <0.05 was considered statistically significant. The levels of inflammatory cytokines were found to be elevated in I-IRI group and depleted in I-IRI+AM group. The biochemical and histopathological markers of injuries at the intestine and remote organs were found to be recuperated when the AM applied before the reperfusion phase. Results of this study demonstrated that the therapeutic drug adrenomedullin (AM) could reverse the intestinal and remote organ injuries related to intestinal ischemic reperfusion injury (I-IRI). These effects might be related to the antioxidant, anti-inflammatory, and anti-apoptotic activities of AM.
ABSTRACT
Objective To investigate the changes of proteins expressions in intestinal mucosa of rats after is chemic postconditioning (IPo) against intestinal ischemic/reperfusion (Ⅱ/R) injury of intestine in order to elucidate its potential mechanisms of protective role. Methods Sixteen SD rats were randomly divided into Ⅱ/R group and IPo group ( n = 8). Rats of both groups received an episode of ischemic/reperfusion insult to intstine that was made by occlusion of the superior mesenteric artery (SMA) for 60 minutes. Rats of IPo group underwent three additional episodes of clamping SMA on for 30 seconds and off for 30 seconds successively after prolonged reperfusion/reperfusion of intestine. The intestinal mucosa was taken by scratching immediately after reperfusion in both groups, and total proteins were separated by immobilized pH gradient (IPG) based two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were analyzed using Image Master 2D Elite 5.0 image analysis software, and the proteins were cut out from the gel and then identified using MALDI-TOF-MS. The biological information of these proteins was looked for in the database of these peptide mass finger-printing (PMF) .Results Ten differentially expressed proteins were found, of which 6 were up-regulated and 4 were down-regulated in IPo group. Nine proteins were identified and characterized by their bioelements including aldose reductase and aldehyde dehydrogenase that were related to anti-oxidative stress and inhibition of cell apoptosis. Conclusions The well-reproducible 2-DE profiles of intestinal mucosa in II/R and IPo groups were established. The potentially protective effects of IPo may be attributed to up-regulating protein expressions of aldose reductase and aldehyde dehydrogenase, and thereby suppressing oxidative stress and cell apoptosis.