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地塞米松和L-刀豆氨酸在实验性脓毒性休克中的比较效果

Comparative effects of dexamethasone and L-canavanine in experimental septic shock.

作者信息

Mansart Arnaud, Bollaert Pierre-Edouard, Levy Bruno, Nicolas Marie-Bénédicte, Mallié Jean-Pierre

机构信息

Laboratoire de Néphrologie Expérimentale (UPRES-JE 2165), Faculté de Médecine, 54 505 Vandoeuvre les, Nancy, France

出版信息

Eur J Pharmacol. 2003 Aug 15;475(1-3):61-7. doi: 10.1016/s0014-2999(03)02035-1.

Abstract

Glucocorticoids can reverse hemodynamic disturbances and dependence on catecholamines in septic shock. The relevant beneficial mechanisms of steroids in septic shock are unknown, although inducible nitric oxide synthase could account for them. The aim of this study was to compare the effects of dexamethasone, a glucocorticoid and L-canavanine, a selective inhibitor of inducible nitric oxide synthase, in a rodent model of sepsis. Mean arterial pressure was restored by dexamethasone and L-canavanine administration at 24 h, no longer at 30 h. Dexamethasone but not L-canavanine improved aortic blood flow at 24 and 30 h. Although both dexamethasone and L-canavanine administration significantly reduced nitrite/nitrate production, and improved survival, steroids did better for survival. In conclusion, dexamethasone and L-canavanine displayed similar vasopressor effects. In addition, steroids improved blood flow suggesting that steroid-induced hemodynamic improvement in sepsis is not solely due to inhibition of inducible nitric oxide synthase.

摘要

糖皮质激素可逆转脓毒症休克中的血流动力学紊乱及对儿茶酚胺的依赖。尽管诱导型一氧化氮合酶可能是其相关作用机制,但糖皮质激素在脓毒症休克中的有益机制尚不清楚。本研究旨在比较糖皮质激素地塞米松和诱导型一氧化氮合酶选择性抑制剂L-刀豆氨酸在啮齿动物脓毒症模型中的作用。地塞米松和L-刀豆氨酸给药后24小时平均动脉压恢复,30小时时不再恢复。地塞米松而非L-刀豆氨酸在24小时和30小时时改善了主动脉血流。尽管地塞米松和L-刀豆氨酸给药均显著降低了亚硝酸盐/硝酸盐生成并改善了生存率,但糖皮质激素对生存率的改善效果更好。总之,地塞米松和L-刀豆氨酸表现出相似的升压作用。此外,糖皮质激素改善了血流,提示糖皮质激素诱导的脓毒症血流动力学改善并非仅归因于对诱导型一氧化氮合酶的抑制。

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