Hattori Y, Akimoto K, Nakanishi N, Kasai K
Department of Endocrinology, Dokkyo University School of Medicine, Tochigi, Japan.
Biochem Biophys Res Commun. 1997 Nov 17;240(2):298-303. doi: 10.1006/bbrc.1997.7653.
Wistar rats injected intravenously with bacterial lipopolysaccharide (LPS) developed endotoxic shock with severe hypotension, significantly elevated concentrations of NOx (nitrate and nitrite) and biopterin in the plasma, and lung expression of high levels of the mRNAs for inducible NO synthase (iNOS) and GTP cyclohydrolase I (GTPCH). Pretreatment of the rats with dexamethasone (DEX) prevented the hypotension, attenuated the increase in plasma NOx and biopterin concentrations, and significantly inhibited the increase in lung biopterin content caused by LPS treatment. DEX also inhibited the induction of iNOS mRNA but not GTPCH mRNA. Adrenalectomized (ADX) rats developed a more severe form of circulatory shock in response to low-dose LPS accompanied by a substantial increase in circulating NOx as well as biopterin, which was prevented by pretreatment with DEX. Thus, glucocorticoids may protect against endotoxic shock by inhibiting the induction of NO synthesis, not only by attenuating iNOS protein induction but also by limiting biopterin availability. Although endogenous glucocorticoids may inhibit the production of NO as well as biopterin after LPS in rats, the mechanisms for these effects appear to be different.
经静脉注射细菌脂多糖（LPS）的Wistar大鼠会发生内毒素休克，伴有严重低血压、血浆中NOx（硝酸盐和亚硝酸盐）和生物蝶呤浓度显著升高，以及肺组织中诱导型一氧化氮合酶（iNOS）和GTP环化水解酶I（GTPCH）的mRNA高水平表达。用地塞米松（DEX）预处理大鼠可预防低血压，减轻血浆NOx和生物蝶呤浓度的升高，并显著抑制LPS处理引起的肺生物蝶呤含量增加。DEX还抑制iNOS mRNA的诱导，但不抑制GTPCH mRNA的诱导。肾上腺切除（ADX）大鼠对低剂量LPS会产生更严重的循环休克形式，同时循环中的NOx和生物蝶呤大幅增加，而DEX预处理可预防这种情况。因此，糖皮质激素可能通过抑制NO合成的诱导来预防内毒素休克，这不仅是通过减弱iNOS蛋白的诱导，还通过限制生物蝶呤的可利用性。虽然内源性糖皮质激素可能在大鼠LPS处理后抑制NO以及生物蝶呤的产生，但其作用机制似乎有所不同。
