Effects of HIF-1α agonist or inhibitor on intestinal mucosal permeability in rats with sepsis

Objective To investigate the effects of sepsis and HIF-1α agonist or inhibitor on intestinal mucosal barrier function. Methods SD rats were randomly divided into sham operation group (sham), Sepsis group treating with cecal ligation and perforation (CLP), Sepsis+HIF-1α agonist group (sepsis + DMOG) receiving intraperitoneal injection of HIF-1α agonist DMOG (40 mg/kg) for 7 consecutive days before CLP, Sepsis+HIF-1α inhibitor group (sepsis+BAY87-2243) orally administered with HIF-1α inhibitor BAY87-2243 (9 mg/kg) for 3 consecutive days before CLP. There were 6 rats in each group. Plasma intestinal permeability markers of diamine oxidase (DAO), intestinal type fatty acid binding protein 2 (FABP2), D-Lactic acid and fluorescein isothiocyanate–dextran (FD4) were detected by ELISA. Morphological changes of intestinal mucosa were detected by HE staining. HIF-1α and TJs protein expression were detected by Western blot. Results Sepsis caused pathological damage, increased permeability (P < 0.05), up-regulation of HIF-1α and down-regulation of tight junctions (TJs) expression in intestinal mucosa of rats with sepsis (P < 0.05); addition of DMOG alleviated intestinal mucosal pathological damage and decreased intestinal permeability (P < 0.05); while rats treated with BAY87-2243 showed the opposite result. Conclusions HIF-1α agonist can significantly reduce intestinal mucosal permeability in sepsis rats, and its inhibitor has the opposite effect. It is suggested that HIF-1α upregulation may protect intestinal mucosa from sepsis.