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谷氨酰胺可保护离体鼠肺缺血再灌注诱导的急性肺损伤。

Glutamine protects ischemia-reperfusion induced acute lung injury in isolated rat lungs.

机构信息

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.

出版信息

Pulm Pharmacol Ther. 2011 Feb;24(1):153-61. doi: 10.1016/j.pupt.2010.07.002. Epub 2010 Aug 3.

Abstract

Glutamine has been used to treat a number of diseases via modulating the inflammatory response. The purpose of this study is to investigate whether glutamine has a beneficial effect in ischemia-reperfusion (IR) induced acute lung injury in an isolated rat lung model. Typical acute lung injury in rats was successfully induced by 60 min of ischemia and 60 min of reperfusion. At the end of experiment, bronchoalveolar lavage fluid (BALF), perfusate and lung tissues were collected to evaluate the degree of lung injury. Glutamine (20 mM) was administrated before ischemia or after ischemia. IR caused a significant increase in the capillary filtration coefficient; lung weight gain; lung weight to body weight ratio; wet to dry weight ratio; pulmonary arterial pressure; and protein concentration and lactate dehydrogenase level in BALF. Tumor necrosis factor-α and cytokine induced neutrophil chemoattractant-1 in perfusate, and malondialdehyde levels, carbonyl content and myeloperoxidase activities in lung tissue were also significantly increased. In addition, the lung tissues showed increased septal thickness and neutrophil infiltration. Furthermore, NF-κB activity and degradation of IκB-α were significantly increased in the lungs. Treatment with glutamine before ischemia or after ischemia significantly decreased the increase in these parameters. Our study showed that glutamine treatment decreased IR-induced acute lung injury. The protective mechanism may be due to the inhibition of NF-κB activation and the attenuation of oxidative stress.

摘要

谷氨酰胺通过调节炎症反应已被用于治疗多种疾病。本研究旨在探讨谷氨酰胺在离体大鼠肺模型中对缺血再灌注(IR)诱导的急性肺损伤是否具有有益作用。通过 60 分钟的缺血和 60 分钟的再灌注成功诱导了典型的急性肺损伤大鼠。在实验结束时,收集支气管肺泡灌洗液(BALF)、灌洗液和肺组织,以评估肺损伤程度。在缺血前或缺血后给予谷氨酰胺(20mM)。IR 导致毛细血管滤过系数显著增加;肺重量增加;肺重/体重比;湿重/干重比;肺动脉压;BALF 中蛋白浓度和乳酸脱氢酶水平升高。在灌洗液中肿瘤坏死因子-α和细胞因子诱导的中性粒细胞趋化因子-1,以及肺组织中的丙二醛水平、羰基含量和髓过氧化物酶活性也显著增加。此外,肺组织显示间隔增厚和中性粒细胞浸润增加。此外,NF-κB 活性和 IκB-α的降解在肺部明显增加。缺血前或缺血后给予谷氨酰胺治疗可显著降低这些参数的增加。我们的研究表明,谷氨酰胺治疗可减轻 IR 诱导的急性肺损伤。保护机制可能归因于 NF-κB 激活的抑制和氧化应激的减轻。

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