Background
Postconditioning may prove to be a suitable method to decrease ischemia-reperfusion
injury of intestine after mesenteric arterial occlusion. Toll-like-receptor-4 is involved
in the pathophysiology of organ damage after ischemia-reperfusion; therefore, the
aim of our study was to investigate the effect of postconditioning on the mucosal
expression of toll-like-receptor-4.
Methods
Male Wistar rats (n = 10/group) underwent 60 minutes of superior mesenteric artery occlusion followed
by 6 hours of reperfusion in 3 groups: sham-operated, ischemia-reperfusion, and a
postconditioned group. Postconditioning was performed by 6 alternating cycles of 10 seconds
of reperfusion/reocclusion. Blood and tissue samples were collected at the end of
reperfusion. Intestinal histopathologic changes and immunohistochemical expression
of mucosal caspase-3, antioxidant status, and protein levels of high-mobility group
box-1 and toll-like-receptor-4 were assessed. Immunofluorescent labeling and confocal
microscopic analysis of toll-like-receptor-4 were performed. Mucosal and serum levels
of interleukin-6 and tumor necrosis factor-α protein were measured.
Results
Histologic alterations in the postconditioned group were associated with decreased
caspase-3 positivity, less toll-like-receptor-4 mRNA, and less protein expression
of high-mobility group box-1 and toll-like-receptor-4 in the intestinal villi compared
with the ischemia-reperfusion group. Furthermore, a significantly improved antioxidant
state of the intestinal mucosa and less mucosal and serum protein levels of interleukin-6
and tumor necrosis factor-α were detected in the postconditioned group.
Conclusion
Small intestinal ischemia-reperfusion injury in male Wistar rats caused by the occlusion
of the superior mesenteric artery was ameliorated by the use of postconditioning,
showing a more favorable inflammatory response, which may be attributed to the decreased
mucosal expression of toll-like-receptor-4.
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References
- AGA technical review on intestinal ischemia.Gastroenterology. 2000; 118: 954-968
- Acute mesenteric ischemia: classification, evaluation and therapy.Acta Gastroenterol Belg. 2002; 65: 220-225
- DAMPening inflammation by modulating TLR signalling.Mediators Inflamm. 2010; 2010: 1-21
- HMGB1 contributes to kidney ischemia reperfusion injury.J Am Soc Nephrol. 2010; 21: 1878-1890
- Linking oxidative stress to inflammation: Toll-like receptors.Free Radic Biol Med. 2010; 48: 1121-1132
- Involvement of reactive oxygen species in Toll-like receptor 4-dependent activation of NF-kappa B.J Immunol. 2004; 172: 2522-2529
- The HMGB1-TLR4 axis contributes to myocardial ischemia/reperfusion injury via regulation of cardiomyocyte apoptosis.Gene. 2013; 527: 389-393
- Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain.J Neurosci Res. 2008; 86: 1125-1131
- TLR4-HMGB1-, MyD88- and TRIF-dependent signaling in mouse intestinal ischemia/reperfusion injury.World J Gastroenterol. 2015; 21: 8314-8325
- Expression and involvement of Toll-like receptors (TLR)2, TLR4, and CD14 in monocyte TNF-alpha production induced by lipopolysaccharides from Neisseria meningitidis.Med Sci Monit. 2003; 9: BR316-BR324
- Intestinal ischemia-reperfusion of macaques triggers a strong innate immune response.World J Gastroenterol. 2014; 20: 15327-15334
- Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis.Cell. 2004; 118: 229-241
- Intestinal epithelial toll-like receptors: to protect. And serve?.Curr Pharm Des. 2003; 9: 1-5
- Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning.Am J Physiol Heart Circ Physiol. 2003; 285: H579-H588
- Postconditioning the human heart.Circulation. 2005; 112: 2143-2148
- Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal.Arch Surg. 1970; 101: 478-483
- Postconditioning of the small intestine: which is the most effective algorithm in a rat model?.J Surg Res. 2014; 187: 427-437
- The effects of n-3 PUFA and intestinal lymph drainage on high-mobility group box 1 and Toll-like receptor 4 mRNA in rats with intestinal ischaemia-reperfusion injury.Br J Nutr. 2012; 108: 883-892
- Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/reperfusion injury to the rat intestinal epithelium.Gut. 1998; 42: 530-537
- Toll-like receptor 4 is protective against neonatal murine ischemia-reperfusion intestinal injury.J Pediatr Surg. 2010; 45: 1246-1255
- Comparison of immunohistochemistry for activated caspase-3 and cleaved cytokeratin 18 with the TUNEL method for quantification of apoptosis in histological sections of PC-3 subcutaneous xenografts.J Pathol. 2003; 199: 221-228
- Ischemic postconditioning during reperfusion attenuates oxidative stress and intestinal mucosal apoptosis induced by intestinal ischemia/reperfusion via aldose reductase.Surgery. 2013; 153: 555-564
- Effects of antioxidative agents on apoptosis induced by ischaemia-reperfusion in rat intestinal mucosa.Aliment Pharmacol Ther. 2003; 18: 139-145
- Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion.Cardiovasc Res. 2004; 62: 74-85
- Ischemic postconditioning protects the spinal cord from ischemia-reperfusion injury via modulation of redox signaling.J Thorac Cardiovasc Surg. 2013; 146: 688-695
- Ischemic postconditioning modified renal oxidative stress and lipid peroxidation caused by ischemic reperfusion injury in rats.Transplant Proc. 2009; 41: 3597-3602
- The immune response of germ-free piglets after peroral monocontamination with living Escherichia coli strain 086. I. The fate of antigen, dynamics and site of antibody formation, nature of antibodies and formation of heterohaemagglutinins.Folia Biol (Praha). 1970; 16: 177-187
- Endogenous toll-like receptor ligands and their biological significance.J Cell Mol Med. 2010; 14: 2592-2603
- Role of HMGB1 in apoptosis-mediated sepsis lethality.J Exp Med. 2006; 203: 1637-1642
- Inhibition of Toll-like receptor 4 with vasoactive intestinal peptide attenuates liver ischemia-reperfusion injury.Transplant Proc. 2011; 43: 1462-1467
- Protective effects of Toll-like receptor 4 inhibitor eritoran on renal ischemia-reperfusion injury.Transplant Proc. 2010; 42: 1539-1544
- Remote ischemic postconditioning protects ischemic brain from injury in rats with focal cerebral ischemia/reperfusion associated with suppression of TLR4 and NF-small ka, CyrillicB expression.Neuroreport. 2016; 27: 469-475
- Toll-like receptor-4 is required for intestinal response to epithelial injury and limiting bacterial translocation in a murine model of acute colitis.Am J Physiol Gastrointest Liver Physiol. 2005; 288: G1055-G1065
- A novel Toll-like receptor 4 antagonist antibody ameliorates inflammation but impairs mucosal healing in murine colitis.Am J Physiol Gastrointest Liver Physiol. 2009; 296: G1167-G1179
- Intestinal ischemia/reperfusion injury triggers activation of innate toll-like receptor 4 and adaptive chemokine programs.Transplant Proc. 2008; 40: 3339-3341
- Intestinal cytokine response after gut ischemia: role of gut barrier failure.Ann Surg. 1999; 229: 478-486
- Ischemic post-conditioning to counteract intestinal ischemia/reperfusion injury.World J Gastrointest Pathophysiol. 2010; 1: 137-143
- Immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS).Ann Intern Med. 1996; 125: 680-687
- Gender differences in ischemia-reperfusion-induced microcirculatory and epithelial dysfunctions in the small intestine.Life Sci. 2006; 78: 3058-3065
- The interaction between gut microbiota and age-related changes in immune function and inflammation.Immun Ageing. 2013; 10: 31
- Postconditioning and protection from reperfusion injury: where do we stand? Position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology.Cardiovasc Res. 2010; 87: 406-423
- Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning.Pharmacol Rev. 2014; 66: 1142-1174
Article info
Publication history
Published online: November 11, 2016
Accepted:
September 22,
2016
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.