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氧衍生自由基在实验性休克发病机制中的作用

Oxygen-derived free radicals in the pathogenesis of experimental shock.

作者信息

Novelli G P, Angiolini P, Livi P, Paternostro E

机构信息

Institute of Anesthesiology and I.T., University of Florence, Careggi Hospital, Italy.

出版信息

Resuscitation. 1989 Dec;18(2-3):195-205. doi: 10.1016/0300-9572(89)90022-1.

DOI:10.1016/0300-9572(89)90022-1
PMID:2555873
Abstract

Oxygen-derived free radicals are naturally produced in biological systems mostly in ischemia and hypoxia related conditions. Imbalance of physiological defenses against oxygen-derived free radicals causes cellular damage. In our laboratory the role of oxygen radicals in the pathogenesis of circulatory shock was studied by exploiting the scavenging action of the spin-trapping compound phenyl-butyl-nitrone (PBN) in experiments concerning: (1) survival after shock, (2) microcirculatory derangements in endotoxin shock, (3) fluidity modifications of cell membranes during shock, (4) exhalation of ethane as non-invasive marker of shock. In some experiments the steroid methylprednisolone was used. Results showed that administration of PBN and of the steroid (1) ensures survival after otherwise lethal shock as confirmed by decreased ethane exhalation, (2) prevents microcirculatory troubles, (3) maintains stability of cell membranes. These findings strongly support the role of oxygen-derived free radicals in the pathogenesis and pathophysiology of circulatory shock.

摘要

氧衍生自由基在生物系统中主要在与缺血和缺氧相关的情况下自然产生。针对氧衍生自由基的生理防御失衡会导致细胞损伤。在我们实验室中,通过利用自旋捕获化合物苯基丁基硝酮(PBN)的清除作用,在以下实验中研究了氧自由基在循环性休克发病机制中的作用:(1)休克后的存活率,(2)内毒素休克中的微循环紊乱,(3)休克期间细胞膜流动性的改变,(4)乙烷呼出作为休克的非侵入性标志物。在一些实验中使用了类固醇甲基强的松龙。结果表明,给予PBN和类固醇:(1)如乙烷呼出减少所证实的那样,确保了在原本致命的休克后存活,(2)预防了微循环问题,(3)维持了细胞膜的稳定性。这些发现有力地支持了氧衍生自由基在循环性休克发病机制和病理生理学中的作用。

相似文献

1
Oxygen-derived free radicals in the pathogenesis of experimental shock.氧衍生自由基在实验性休克发病机制中的作用
Resuscitation. 1989 Dec;18(2-3):195-205. doi: 10.1016/0300-9572(89)90022-1.
2
Oxygen radicals in experimental shock: effects of spin-trapping nitrones in ameliorating shock pathophysiology.实验性休克中的氧自由基:自旋捕获硝酮对改善休克病理生理学的作用。
Crit Care Med. 1992 Apr;20(4):499-507. doi: 10.1097/00003246-199204000-00012.
3
Ethane in expired air during shock in rats.大鼠休克期间呼出气体中的乙烷
Prog Clin Biol Res. 1988;264:397-402.
4
Phenyl-T-butyl-nitrone is active against traumatic shock in rats.苯基叔丁基硝酮对大鼠创伤性休克有活性作用。
Free Radic Res Commun. 1986;1(5):321-7. doi: 10.3109/10715768609080971.
5
Protective effects of a cyclic nitrone antioxidant in animal models of endotoxic shock and chronic bacteremia.一种环状硝酮抗氧化剂在内毒素休克和慢性菌血症动物模型中的保护作用。
Circ Shock. 1994 Jul;43(3):130-6.
6
Modification by oxygen free radical scavengers of the metabolic and cardiovascular effects of endotoxin infusion in conscious rats.氧自由基清除剂对清醒大鼠内毒素输注的代谢和心血管效应的影响
Circ Shock. 1986;19(4):429-39.
7
Oxygen radicals scavenging in prophylaxis and treatment of experimental shock.氧自由基清除在实验性休克预防和治疗中的作用
Prog Clin Biol Res. 1987;236A:259-69.
8
Demonstration of free radical generation in "stunned" myocardium of intact dogs with the use of the spin trap alpha-phenyl N-tert-butyl nitrone.使用自旋捕捉剂α-苯基-N-叔丁基硝酮证明完整犬“顿抑”心肌中自由基的产生。
J Clin Invest. 1988 Aug;82(2):476-85. doi: 10.1172/JCI113621.
9
Spin trapping agent, phenyl N-tert-butyl nitrone, inhibits induction of nitric oxide synthase in endotoxin-induced shock in mice.自旋捕捉剂苯基 N-叔丁基硝酮可抑制小鼠内毒素诱导性休克中一氧化氮合酶的诱导。
Biochem Biophys Res Commun. 1995 Oct 4;215(1):114-21. doi: 10.1006/bbrc.1995.2440.
10
Spin-trapping studies of hepatic free radicals formed following the acute administration of ethanol to rats: in vivo detection of 1-hydroxyethyl radicals with PBN.
Free Radic Biol Med. 1991;11(1):31-9. doi: 10.1016/0891-5849(91)90185-6.

引用本文的文献

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Potential implication of the chemical properties and bioactivity of nitrone spin traps for therapeutics.氮氧自由基捕获剂的化学性质和生物活性对治疗的潜在影响。
Future Med Chem. 2012 Jun;4(9):1171-207. doi: 10.4155/fmc.12.74.
2
Effects of endotoxic shock in several functions of murine peritoneal macrophages.内毒素休克对小鼠腹腔巨噬细胞多种功能的影响。
Mol Cell Biochem. 1998 Dec;189(1-2):25-31. doi: 10.1023/a:1006891926301.
3
Improved survival and reversal of endothelial dysfunction by the 21-aminosteroid, U-74389G in splanchnic ischaemia-reperfusion injury in the rat.
21-氨基类固醇U-74389G改善大鼠内脏缺血再灌注损伤后的生存率并逆转内皮功能障碍。
Br J Pharmacol. 1995 Jun;115(3):395-400. doi: 10.1111/j.1476-5381.1995.tb16346.x.