Kotani Tohru, Komatsu Yoshino, Nakamori Yuka, Takeuchi Koji
Life Sci. 2009 Apr 24;84(17-18):615-21.
We established a new model of ischemic enteritis in rats and evaluated its usefulness for screening prophylactic drugs.
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.
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).
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.
我们建立了一种新的大鼠缺血性肠炎模型,并评估其在筛选预防性药物方面的实用性。
雄性SD大鼠禁食18小时后使用。在乙醚麻醉下,暴露肠系膜上动脉(SMA),通过将一根针置于血管上、结扎血管和针,然后从结扎处取出针来制造校准狭窄。
狭窄在3天内导致小肠系膜对侧严重损伤;损伤严重程度随针的规格增加而增加。使用小于21号的针进行狭窄操作后,小肠未发生损伤。使用23号针时,多发性出血性病变的发生率为100%。肠炎的发展伴随着黏膜中肠细菌的侵袭,诱导型一氧化氮合酶(iNOS)表达上调和一氧化氮(NO)产生增加。用氨基胍(一种选择性iNOS抑制剂)、L-精氨酸甲酯(一种非选择性NOS抑制剂)、氨苄西林和氨曲南(一种革兰氏阴性菌抗生素)重复治疗可显著预防缺血性肠炎,但万古霉素(一种革兰氏阳性菌抗生素)无效。
这些结果表明,通过SMA狭窄在大鼠中诱导出一种新型缺血性肠炎模型,该模型可能有助于筛选抗缺血性肠炎药物,并且革兰氏阴性菌以及iNOS/NO参与了该模型中肠炎的发病机制。