Glutamine induces heat shock protein and protects against endotoxin shock in the rat
Glutamine induces heat shock protein and protects against endotoxin shock in the rat
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DOI：
10.1152/jappl.2001.90.6.2403
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发表时间：
2001-06-01
影响因子：
3.3
通讯作者：
Chang, EB
中科院分区：
文献类型：
--
作者：
Wischmeyer, PE;Kahana, M;Chang, EB
热休克蛋白（HSP）的表达增强已被证明是对实验室模型的感染性休克的保护。诱导HSP以改善人类疾病的结果尚未被利用，因为实验室诱导剂本身是有毒的，并且与临床无关。在这项研究中，我们证明，一个单一剂量的静脉注射谷氨酰胺导致快速和显着增加HSP 25和HSP 72在多个器官的非应激Sprague-Dawley大鼠的表达。利用液体复苏的内毒素血症大鼠模型，谷氨酰胺给药伴随内毒素损伤可显著降低死亡率。给予谷氨酰胺的内毒素处理的动物表现出组织HSP表达的显著增加和终末器官损伤的显着减少。这些数据表明，谷氨酰胺可以通过增强HSP表达来防止死亡和减轻内毒素休克中的终末器官损伤。此外，谷氨酰胺在脓毒症开始时给药，而不是作为预处理时给予保护。因此，谷氨酰胺似乎是一种临床上可行的HSP表达增强剂，并可能证明有益于脓毒症和脓毒症诱导的器官损伤的治疗。
Enhanced expression of heat shock protein (HSP) has been shown to be protective against laboratory models of septic shock. Induction of HSPs to improve outcome in human disease has not been exploited because laboratory induction agents are themselves toxic and not clinically relevant. In this study, we demonstrate that a single dose of intravenous glutamine causes a rapid and significant increase in HSP25 and HSP72 expression in multiple organs of the unstressed Sprague-Dawley rat. With the utilization of a fluid-resuscitated rat model of endotoxemia, mortality was dramatically reduced by glutamine administration concomitant with the endotoxin injury. Endotoxin-treated animals given glutamine exhibited dramatic increases in tissue HSP expression and marked reduction of end-organ damage. These data suggest glutamine may protect against mortality and attenuate end-organ injury in endotoxemic shock via enhanced HSP expression. Furthermore, glutamine confers protection when administered at the initiation of sepsis, rather than as pretreatment. Thus glutamine appears to be a clinically viable enhancer of HSP expression and may prove beneficial in the therapy of sepsis and sepsis-induced organ injury.