Glutamine administration ameliorates sepsis-induced kidney injury by downregulating the high-mobility group box protein-1-mediated pathway in mice
Glutamine administration ameliorates sepsis-induced kidney injury by downregulating the high-mobility group box protein-1-mediated pathway in mice
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DOI：
10.1152/ajprenal.00246.2011
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发表时间：
2012-01-01
影响因子：
4.2
通讯作者：
Yeh, Sung-Ling
中科院分区：
文献类型：
--
作者：
Hu, Ya-Mei;Pai, Man-Hui;Yeh, Sung-Ling
胡延明，派MH，叶春林，侯永成，叶世林。谷氨酰胺通过下调小鼠高迁移率族蛋白-1介导的通路改善脓毒症诱导的肾损伤。美国肾脏生理学杂志302：F150-F158，2012年。首次发表于2011年9月14日; doi：10.1152/ajprenal.00246.2011。急性肾损伤（阿基）是脓毒症的严重并发症。高迁移率族蛋白（HMGB）-1被认为是脓毒症致死性全身炎症的晚期介质。由于谷氨酰胺（GLN）被证明具有抗炎和抗氧化特性，我们假设GLN给药可能下调HMGB-1介导的通路，从而改善脓毒症诱导的阿基。将小鼠随机分配到正常组（NC）、脓毒性盐水组（SS）或脓毒性GLN组（SG）。通过盲肠结扎穿孔（CLP）诱导脓毒症。SS组于CLP后1h尾静脉注射生理盐水，SG组于CLP后1h尾静脉注射GLN 0.75g/kg体重。CLP后2、6和24 h处死小鼠，收获动物的血液和肾脏用于进一步分析。结果显示，与正常小鼠相比，脓毒症导致肾脏HMGB-1、toll样受体（TLR）4、骨髓分化初级反应蛋白（MyD）88和晚期糖基化终末产物受体（RAGE）的mRNA和/或蛋白表达升高。给予GLN的脓毒症小鼠表现出HMGB-1、TLR 4、TNF α和磷酸化NF-κ B p65蛋白表达降低，肾组织中硝基酪氨酸水平降低。组织学检查结果显示，SG组的肾脏损伤较轻，存活率提高。这些结果表明，在脓毒症开始后给予单剂量GLN在下调HMGB-1相关介质的表达和降低肾脏中的氧化应激方面起预防作用，这可能因此改善了脓毒症诱导的阿基。
Hu YM, Pai MH, Yeh CL, Hou YC, Yeh SL. Glutamine administration ameliorates sepsis-induced kidney injury by downregulating the high-mobility group box protein-1-mediated pathway in mice. Am J Physiol Renal Physiol 302: F150-F158, 2012. First published September 14, 2011; doi:10.1152/ajprenal.00246.2011.Acute kidney injury (AKI) is a severe complication of sepsis. High-mobility group box (HMGB)-1 was implicated as a late mediator of lethal systemic inflammation in sepsis. Since glutamine (GLN) was shown to have anti-inflammatory and antioxidant properties, we hypothesized that GLN administration may downregulate an HMGB-1-mediated pathway and thus ameliorate sepsis-induced AKI. Mice were randomly assigned to a normal group (NC), a septic saline group (SS), or a septic GLN group (SG). Sepsis was induced by cecal ligation and puncture (CLP). The SS group was injected with saline, and the SG group was given 0.75 g GLN/kg body wt once via a tail vein 1 h after CLP. Mice were killed 2, 6, and 24 h after CLP, and blood and kidneys of the animals were harvested for further analysis. The results showed that sepsis resulted in higher mRNA and/or protein expressions of kidney HMGB-1, toll-like receptor (TLR) 4, myeloid differentiation primary-response protein (MyD) 88, and receptor of advanced glycation end products (RAGE) compared with normal mice. Septic mice with GLN administration exhibited decreased HMGB-1, TLR4, RAGE, and phosphorylated NF-kappa B p65 protein expressions and reduced nitrotyrosine levels in kidney tissues. The histological findings showed that damage to the kidneys was less severe, and survival improved in the SG group. These results indicated that a single dose of GLN administered after the initiation of sepsis plays a prophylactic role in downregulating the expressions of HMGB-1-related mediators and decreasing oxidative stress in the kidneys, which may consequently have ameliorated AKI induced by sepsis.