Role of endogenous peroxisome proliferator-activated receptor-α (PPAR-α) ligands in the development of gut ischemia and reperfusion in mice

The peroxisome proliferator-activated receptor-α (PPAR-α) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid, and thyroid hormone receptors. The aim of the present study was to examine the effects of endogenous PPAR-α ligand on the development of gut ischemia and reperfusion injury. Splanchnic artery occlusion (SAO) shock was induced in mice by clamping both the superior mesenteric artery and the celiac artery for 30 min, followed thereafter by release of the clamp (reperfusion). At 60 min after reperfusion, animals were sacrificed for histological examination and biochemical studies. SAO-shocked WT mice developed a significant increase of ileum tissue, TNF-α, IL-1β, myeloperoxidase activity, and marked histological injury. SAO shock was also associated with a significant mortality (0% survival at 24 h after reperfusion). Reperfused ileum tissue sections from SAO-shocked WT mice showed positive staining for P-selectin, ICAM-1, TNF-α, and IL-1β. Absence of a functional PPAR-α gene in PPAR-αKO mice resulted in a significant augmentation of all the above-described parameters. Thus, endogenous PPAR-α ligands reduce the degree of ileum injury caused by ischemia and reperfusion.