Protective effect of thiaton, an antispasmodic drug, against indomethacin-induced intestinal damage in rats
Protective effect of thiaton, an antispasmodic drug, against indomethacin-induced intestinal damage in rats
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DOI：
10.1254/jjp.88.45
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Takeuchi, K
中科院分区：
文献类型：
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作者：
Kunikata, T;Miyazawa, T;Takeuchi, K
本文观察了噻托溴铵[3-（二-2-噻吩亚甲基）-5-甲基-反式-溴化喹嗪]对吲哚美辛所致大鼠肠损伤的作用。动物皮下注射消炎痛，24小时后检查肠粘膜。皮下注射Thiaton或阿托品。两次，消炎痛前30 min和消炎痛后8 h。吲哚美辛可引起肠道损伤，并伴有肠细菌移位以及诱导型一氧化氮合酶（iNOS）和髓过氧化物酶（MPO）活性的增加，补充16，16-二甲基前列腺素E-2（dmPGE（2））可显著预防这些变化。噻托溴铵剂量依赖性地预防了动物的肠损伤，同时抑制了MPO和iNOS活性，阿托品也观察到了类似的效果。与dmPGE相似，噻托溴铵和阿托品也显著阻止了细菌移位的增加（2）。吲哚美辛可增强肠蠕动，而噻托溴铵、阿托品或dmPGE可抑制这种作用（2）。吲哚美辛可减少肠粘液和液体分泌，但dmPGE可增强肠粘液和液体分泌（2）。在基础条件下，噻托溴铵和阿托品均轻微降低了这些分泌物，但显著逆转了吲哚美辛引起的分泌物减少。这些结果表明，噻托溴铵保护小肠免受吲哚美辛诱导的损伤和炎症变化，这种作用与预防肠细菌移位有关，该过程与抑制吲哚美辛引起的肠运动亢进有关，可能是由于抗毒蕈碱作用。
The effect of thiaton [3-(di-2-thienylmethylene)-5-methyl-trans-quinolizidinium bromide], an antispasmodic drug, on indomethacin-induced intestinal damage was examined in rats. The animals were given indomethacin, s.c., and the intestinal mucosa was examined 24 It later. Thiaton or atropine was given s.c. twice, 30 min before and 8 h following indomethacin. Indomethacin caused intestinal damage, accompanied with increase in enterobacterial translocation as well as inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) activities, and these changes were significantly prevented by supplementation with 16,16-dimethyl prostaglandin E-2 (dmPGE(2)). Treatment of the animals with thiaton dose-dependently prevented the intestinal damage, together with the suppression of MPO and iNOS activities, and these effects were similarly observed by atropine. The increase of bacterial translocation was also significantly prevented by both thiaton and atropine, similar to dmPGE(2). Indomethacin enhanced intestinal motility, and this effect was inhibited by either thiaton, atropine or dmPGE(2). The intestinal mucus and fluid secretions were decreased by indomethacin but enhanced by dmPGE(2). Both thiaton and atropine slightly decreased these secretions under basal conditions but significantly reversed the decrease in the secretions caused by indomethacin. These results suggest that thiaton protects the small intestine against indomethacin-induced damage and inflammatory changes, and this effect is related with prevention of enterobacterial translocation, the process being associated with inhibition of intestinal hypermotility caused by indomethacin, probably due to anti-muscarinic action.