OP011 N-3 PUFAS PREVENT THE DESTRUCTION OF INTESTINAL BARRIER AFTER ISCHEMIA/REPERFUSION INJURY BY l-FABP INDUCING THE PPARγ PATHWAY ACTIVATION

Abstract

Rationale: This study was designed to investigate whether altered expression of tight junctions (TJs) proteins in intestinal membrane in ischemia/reperfusion injury was prevented by n-3 PUFAs, and the molecular mechanism underlying this beneficial effect. Methods: 24 Male SD rats were assigned to 4 groups: control group (group 1), I/R injury group (group 2), pretreated with n-3PUFAs for 7 days before I/R model was performed (group 3), pretreated with PPARg agonist (15dPGJ2) 30 minutes before I/R injury (group 4). The serum samples were collected for ELISA test, and intestinal mucosa samples were collected for TEM, western blotting and EMSA analysis. Results: After I/R injury, the structure of TJs was disrupted and the expression of occludin decreased. The serum intestinal fatty acid binding protein (IFABP) elevated and the expression of intracellular I-FABP decreased. The expression of activated PPARg in nucleus was attenuated. Pretreatment with n-3PUFAs and 15dPGJ2 reduced the serum level of I-FABP and kept TJs morphology intact comparing with group 2. The expression of occludin and the activated PPARg were both improved in group 3 and 4. Moreover, the expression of cytoplasmic I-FABP was increased in group 3. Conclusion: The intestinal barrier is severely destroyed after I/R injury, which is related to the redistribution of I-FABP. Our findings for the first time indicate that n-3PUFAs can protect the intestinal barrier by modifying intracellular I-FABP, transporting n-3 PUFAs from cytoplasm to nuclei, activating the PPARg pathway in nuclei, and then up regulating the expression of TJ proteins of the intestinal barrier.