O. Rosero1, P. Onody1, T. Kovacs1, A. Fulop1, D. Molnar2, T. Balazsa2, G. Lotz3, L. Harsanyi1, A. Szijarto1 1Semmelweis University,1st Department Of Surgery,Budapest, , Hungary 2Semmelweis University,Department Of Human Morphology And Developmental Biology,Budapest, , Hungary 3Semmelweis University,2nd Department Of Pathology,Budapest, , Hungary
Introduction: Postconditioning is a suitable method to reduce ischemia-reperfusion (IR) induced injury of the intestine following mesenteric arterial occlusion. Toll-like-receptor (TLR)-4 was shown to be involved in the pathophysiology of organ damage after IR, therefore the aim of our study was to investigate the effect of postconditioning on the mucosal expression of TLR-4.
Methods: Male Wistar rats (n=10/group) underwent 60 minutes of superior mesenteric artery (SMA) occlusion followed by 6 hours of reperfusion in three groups: sham-operated, IR- and postconditioned-group. Postconditioning was performed by 6 alternating cycles of 10 seconds reperfusion/reocclusion. Blood and tissue samples were collected at the end of reperfusion. Small intestinal histolopathological changes, mucosal cleaved caspase-3, antioxidant status, HMGB-1 and TLR-4 expression rates were assessed. Mucosal and serum IL-6 and TNF-α levels were measured.
Results: Milder histological alterations of the postconditioned-group were associated with significantly (p<0.01) decreased number of caspase-3 positive cells, lower TLR-4 mRNA and significantly (p<0.05) minor amount of HMGB-1 and TLR-4 protein expression in the intestinal villi compared to the IR-group samples. Furthermore, significantly improved antioxidant state of intestinal mucosa and lower mucosal and serum IL-6, TNF-α levels were detected in the postconditioned-group.
Conclusion: Small intestinal IR-injury caused by the occlusion of the SMA was substantially ameliorated by the use of postconditioning, delivering a more favorable inflammatory response, which may partly be attributed to the decreased mucosal expression of TLR-4.