A novel model of ischemic enteritis induced in rats by stenosis of the superior mesenteric artery

Abstract

Aims We established a new model of ischemic enteritis in rats and evaluated its usefulness for screening prophylactic drugs. Main methods Male SD rats were used after 18 h of fasting. Under ether anesthesia, the superior mesenteric artery (SMA) was exposed, and a calibrated stenosis was produced by placing a needle on a blood vessel, ligating both the vessel and needle, and then removing the needle from the ligature. Key findings The stenosis caused severe damage on the anti-mesenteric side of the small intestine within 3 days; the severity of the damage increased with the gauge of a needle. No damage occurred in the small intestine following the stenosis with a needle of less than 21 gauge. Multiple hemorrhagic lesions occurred at an incidence of 100% when a 23-gauge needle was used. The development of enteritis was accompanied by enterobacterial invasion in the mucosa, with an up-regulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. The ischemia-induced enteritis was significantly prevented by repeated treatment with aminoguanidine (a selective iNOS inhibitor), L-NAME (a nonselective NOS inhibitor), ampicillin, and aztreonam (a gram-negative bacterium antibiotic), but not vancomycin (a gram-positive bacterium antibiotic). Significance These results showed that a novel model of ischemic enteritis is induced in rats by stenosis of the SMA, this model may be useful for screening drugs against ischemic enteritis, and gram-negative bacteria as well as iNOS/NO are involved in the pathogenesis of enteritis in this model.