Kiang Juliann G, Bowman Phillip D, Wu Brian W, Hampton Nyasa, Kiang Andrew G, Zhao Baiteng, Juang Yuang-Taung, Atkins James L, Tsokos George C
Department of Cellular Injury, Division of Military Casualty Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA.
J Appl Physiol (1985). 2004 Aug;97(2):564-9. doi: 10.1152/japplphysiol.00194.2004. Epub 2004 Apr 16.
The aim of this study was to determine whether hemorrhage affects the levels of a variety of stress-related proteins and whether changes can be inhibited by drugs reported to provide protection from ischemia and reperfusion injury. Male Swiss Webster mice were subjected to a 40% hemorrhage without resuscitation. Western blot analysis indicated that c-Jun (an AP-1 protein), Kruppel-like factor 6 (KFL6), and inducible nitric oxide synthase (iNOS) were upregulated sequentially in that order. Pretreatment of mice with geldanamycin (GA) 16 h before hemorrhage effectively inhibited the expression of the proteins KLF6 and iNOS, whereas caffeic acid phenethyl ester did not. GA pretreatment increased inducible heat shock protein (HSP) 70 but not HSP90 in both sham and hemorrhagic tissues. The overexpressed inducible HSP70 formed complexes with KLF6 and iNOS. These results suggest that GA may be therapeutically useful for reducing hemorrhage-induced injury when used as a presurgical treatment or when added to resuscitation fluids.
本研究的目的是确定出血是否会影响多种应激相关蛋白的水平，以及这些变化是否能被据报道可提供缺血再灌注损伤保护作用的药物所抑制。对雄性瑞士韦伯斯特小鼠进行40%的出血且不进行复苏。蛋白质印迹分析表明，c-Jun（一种AP-1蛋白）、Kruppel样因子6（KFL6）和诱导型一氧化氮合酶（iNOS）依次上调。在出血前16小时用格尔德霉素（GA）预处理小鼠可有效抑制KLF6和iNOS蛋白的表达，而咖啡酸苯乙酯则无此作用。GA预处理在假手术组和出血组组织中均增加了诱导型热休克蛋白（HSP）70的表达，但未增加HSP90的表达。过表达的诱导型HSP70与KLF6和iNOS形成复合物。这些结果表明，GA在作为术前治疗或添加到复苏液中使用时，可能对减轻出血性损伤具有治疗作用。
