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高纯度维生素B2对内毒素诱导的小鼠休克中促炎细胞因子和一氧化氮产生的抑制机制

Inhibitory mechanisms of highly purified vitamin B2 on the productions of proinflammatory cytokine and NO in endotoxin-induced shock in mice.

作者信息

Kodama Kohtarou, Suzuki Mamoru, Toyosawa Toshio, Araki Seiichi

机构信息

Tsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan.

出版信息

Life Sci. 2005 Nov 26;78(2):134-9. doi: 10.1016/j.lfs.2005.04.037. Epub 2005 Aug 19.

Abstract

Inhibitory effects of highly purified vitamin B2 (riboflavin-5'-sodium phosphate, >97%) on the interleukin (IL)-6, macrophage inflammatory protein (MIP)-2 and nitric oxide (NO) in LPS-induced shock mice were evaluated. Vitamin B2 at 20 mg/kg (protective effect on mice mortality induced by LPS), intravenously administered 6 h after LPS injection, significantly decreased the plasma elevated levels of IL-6 and MIP-2 at 9 and 12 h. In addition, vitamin B2 lowered the tissue concentration and the mRNA expression of IL-6 in lung and those of MIP-2 in liver at 9 h. Vitamin B2 also reduced concentration of MIP-2 concentration in lung, and inhibited mRNA expression in kidney, respectively. Vitamin B2 decreased the plasma elevated NO levels in accordance with a reduction in expression of inducible NO synthase (iNOS) both at 21 and 24 h. Accordingly, the reduction in elevated plasma cytokine levels and NO based on the inhibitory effect on local cytokine mRNA expression and iNOS would be responsible for the anti-septic effect of vitamin B2.

摘要

评估了高纯度维生素B2(核黄素-5'-磷酸钠,>97%)对脂多糖(LPS)诱导的休克小鼠白细胞介素(IL)-6、巨噬细胞炎性蛋白(MIP)-2和一氧化氮(NO)的抑制作用。LPS注射后6小时静脉注射20mg/kg的维生素B2(对LPS诱导的小鼠死亡率有保护作用),可显著降低9小时和12小时时血浆中升高的IL-6和MIP-2水平。此外,维生素B2在9小时时降低了肺组织中IL-6的浓度及其mRNA表达,以及肝脏中MIP-2的浓度及其mRNA表达。维生素B2还分别降低了肺组织中MIP-2的浓度,并抑制了肾脏中其mRNA表达。维生素B2在21小时和24小时时均降低了血浆中升高的NO水平,同时诱导型NO合酶(iNOS)的表达也相应降低。因此,基于对局部细胞因子mRNA表达和iNOS的抑制作用,血浆中升高的细胞因子水平和NO的降低可能是维生素B2具有抗感染作用的原因。

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