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氨基酸类药物的新治疗策略:谷氨酸单钠对 NSAID 诱导的肠病的预防和治疗促进作用。

New therapeutic strategy for amino acid medicine: prophylactic and healing promoting effect of monosodium glutamate against NSAID-induced enteropathy.

机构信息

Department of Pharmacology and Experimental Therapeutics, Division of Pathological Sciences, Kyoto Pharmaceutical University, Japan.

出版信息

J Pharmacol Sci. 2012;118(2):131-7. doi: 10.1254/jphs.11r03fm. Epub 2012 Jan 27.

Abstract

We reviewed the effect of monosodium glutamate (MSG) on the development and healing of nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal lesions in rats. Loxoprofen (60 mg/kg, p.o.) induced lesions in the small intestine within 24 h, accompanied by a decrease of Muc2 expression and an increase in enterobacterial invasion and inducible nitric oxide synthase (iNOS) expression. These lesions were prevented when MSG was given as a mixture of powdered food for 5 days before the loxoprofen treatment. This effect of MSG was accompanied by an increase in Muc2 expression / mucus secretion as well as the suppression of bacterial invasion and iNOS expression. These intestinal lesions healed spontaneously within 6 days, but the process was impaired by the repeated administration of low-dose loxoprofen (30 mg/kg) for 5 days after the ulceration, with the decrease of vascular endothelial derived growth factor (VEGF) expression and angiogenesis. The healing-impairing effect of loxoprofen was prevented by feeding 5% MSG for 5 days after the ulceration. These results suggest that MSG not only prevents loxoprofen-induced small intestinal damage but also promotes a healing of these lesions; the former is functionally associated with the increase in Muc2 expression / mucus secretion and the suppression of bacterial invasion and iNOS expression, while the latter is associated with the stimulation of VEGF expression/angiogenesis.

摘要

我们研究了谷氨酸单钠(MSG)对大鼠非甾体抗炎药(NSAID)诱导的小肠损伤的发展和愈合的影响。洛索洛芬(60mg/kg,po)在 24 小时内引起小肠损伤,伴随着 Muc2 表达减少和肠杆菌入侵以及诱导型一氧化氮合酶(iNOS)表达增加。当 MSG 作为粉末食物混合物在洛索洛芬治疗前 5 天给予时,这些损伤得到预防。MSG 的这种作用伴随着 Muc2 表达/粘液分泌的增加以及细菌入侵和 iNOS 表达的抑制。这些肠道损伤在 6 天内自发愈合,但在溃疡后重复给予低剂量洛索洛芬(30mg/kg)5 天会损害愈合过程,伴随着血管内皮生长因子(VEGF)表达和血管生成的减少。溃疡后给予 5%MSG 5 天可预防洛索洛芬的愈合损害作用。这些结果表明,MSG 不仅可以预防洛索洛芬引起的小肠损伤,还可以促进这些损伤的愈合;前者与 Muc2 表达/粘液分泌的增加和细菌入侵以及 iNOS 表达的抑制有关,而后者与 VEGF 表达/血管生成的刺激有关。

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