Abstract: Objective To investigate the effects of sepsis and HIF-1α agonist or inhibitor on intestinal mucosal barrier(IBM) function. Methods SD rats were randomly divided into four groups with 6 in each as follows:sham operation group (sham), sepsis group treated with cecal ligation and perforation (CLP), (sepsis+HIF-1α agonist)/(sepsis+DMOG) group receiving intra-peritoneal injection of HIF-1α agonist DMOG (40 mg/kg) for 7 consecutive days before CLP, (sepsis+HIF-1α inhibitor)/(sepsis+BAY87-2243) group orally administered with HIF-1α inhibitor BAY87-2243(9 mg/kg) for 3 consecutive days before CLP. 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 mucosal per- meability (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, and this effect is significantly counteracted by its inhibitor. It is suggested that HIF-1α upregulation may protect intestinal mucosa aganist sepsis.

Key words: sepsis, intestinal mucosal permeability, hypoxia inducible factor 1α, DMOG, BAY87-2243