A diet containing glycine improves survival in endotoxin shock in the rat
A diet containing glycine improves survival in endotoxin shock in the rat
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DOI：
10.1152/ajpgi.1996.271.1.g97
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发表时间：
1996-07-01
影响因子：
4.5
通讯作者：
Thurman, RG
中科院分区：
文献类型：
--
作者：
Ikejima, K;Iimuro, Y;Thurman, RG
在这项研究中，我们研究了含甘氨酸的饮食（5%）对Sprague-Dawley大鼠体内静脉注射内毒素[大肠杆菌脂多糖（LPS）]引起的死亡率和肝损伤的影响。50%的大鼠喂养对照饮食后24小时内静脉注射LPS（10毫克/公斤）死亡，而喂养大鼠甘氨酸完全防止死亡率和显着降低LPS诱导的血清转氨酶水平升高，肝坏死，肺损伤。由LPS引起的血清肿瘤坏死因子-α（TNF-α）的升高也被甘氨酸喂养显著减弱和延迟。在两次打击模型（肝缺血-再灌注和注射亚致死LPS）中，所有喂食对照饮食的大鼠均死亡，而83%喂食甘氨酸的动物存活，转氨酶显著降低，肝和肺组织学改善。LPS使培养的枯否细胞内Ca ~（2+）浓度（[Ca ~（2+）]（i））升高，甘氨酸几乎完全阻断该作用。甘氨酸最有可能通过防止库普弗细胞中LPS诱导的[Ca 2 +]（i）升高来降低损伤和死亡率，从而最大限度地减少毒性类花生酸和细胞因子的产生。
In this study, we investigated the effects of a glycine-containing diet (5%) on mortality and liver injury due to intravenous injection of endotoxin [Escherichia coli lipopolysaccharide (LPS)] in Sprague-Dawley rats in vivo. Fifty percent of the rats fed control diet died within 24 h after an intravenous injection of LPS (10 mg/kg), whereas feeding the rats glycine totally prevented mortality and markedly reduced an LPS-induced elevation of serum transaminase levels, hepatic necrosis, and lung injury. The elevation in serum tumor necrosis factor-alpha (TNF-alpha) due to LPS was also blunted and delayed significantly by glycine feeding. In a two-hit model (hepatic ischemia-reperfusion and injection of sublethal LPS), all rats fed control diet died, whereas 83% of glycine-fed animals survived with a significant reduction in transaminases and improved liver and lung histology. LPS elevated intracellular Ca2+ concentration ([Ca2+](i)) in cultured Kupffer cells, an effect blocked almost completely by glycine. Glycine most likely reduces injury and mortality by preventing the LPS-induced elevation of [Ca2+](i) in Kupffer cells, thereby minimizing toxic eicosanoid and cytokine production.