Remote ischemic preconditioning attenuates intestinal mucosal damage: insight from a rat model of ischemia–reperfusion injury

Abstract

Background Remote ischemic preconditioning (RIPC) is a phenomenon, whereby repeated, non-lethal episodes of ischemia to an organ or limb exert protection against ischemia–reperfusion (I/R) injury in distant organs. Despite intensive research, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms, especially in the intestine. Aim of this study was to evaluate possible protective effects RIPC on intestinal I/R injury. Methods Thirty rats were randomly assigned to four groups: I/R; I/R + RIPC; Sham; Sham + RIPC. Animals were anesthetized and the superior mesenteric artery was clamped for 30 min, followed by 60 min of reperfusion. RIPC-treated rats received 3 × 5 min of bilateral hindlimb I/R prior to surgery, sham groups obtained laparotomy without clamping. After I/R injury serum/tissue was analyzed for: Mucosal damage, Caspase-3/7 activity, expression of cell stress proteins, hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) production, Hypoxia-inducible factor-1α (HIF-1α) protein expression and matrix metalloproteinase (MMP) activity. Results Intestinal I/R resulted in increased mucosal injury (P < 0.001) and elevated Caspase-3/7 activity (P < 0.001). RIPC significantly reduced the histological signs of intestinal I/R injury (P < 0.01), but did not affect Caspase-3/7 activity. Proteome profiling suggested a RIPC-mediated regulation of several cell stress proteins after I/R injury: Cytochrome C (+ 157%); Cited-2 (− 39%), ADAMTS1 (+ 74%). Serum concentrations of H 2 O 2 and MDA remained unchanged after RIPC, while the reduced intestinal injury was associated with increased HIF-1α levels. Measurements of MMP activities in serum and intestinal tissue revealed an attenuated gelatinase activity at 130 kDa within the serum samples (P < 0.001) after RIPC, while the activity of MMPs within the intestinal tissue was not affected by I/R injury or RIPC. Conclusions RIPC ameliorates intestinal I/R injury in rats. The underlying mechanisms may involve HIF-1α protein expression and a decreased serum activity of a 130 kDa factor with gelatinase activity. Electronic supplementary material The online version of this article (10.1186/s12967-019-1885-4) contains supplementary material, which is available to authorized users.

Primary peritoneal drainage in neonates with necrotizing enterocolitis associated with congenital heart disease: a single experience in a Brazilian tertiary center

“…The relative risk of death in NECCAD was higher than in NECCAS, and it was also higher in NECD compared with NECS; however, the neonates without heart disease presented a higher risk of death than newborns with heart disease. The lower risk of these patients can be explained by their more significant hypoxemia, which could partially represent ischemic preconditioning and, therefore, serve as a protective state against intestinal damage ( 28 ).…”

Integrated analysis of a lncRNA‑mRNA network reveals a potential mechanism underlying necrotizing enterocolitis

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Zinc-induced protective effect for testicular ischemia-reperfusion injury by promoting antioxidation via microRNA-101-3p/Nrf2 pathway

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