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亚致死性下肢缺血后给予谷氨酰胺可减轻炎症反应并为缺血/再灌注损伤提供器官保护。

Glutamine Administration After Sublethal Lower Limb Ischemia Reduces Inflammatory Reaction and Offers Organ Protection in Ischemia/Reperfusion Injury.

作者信息

Shih Yao-Ming, Shih Juey-Ming, Pai Man-Hui, Hou Yu-Chen, Yeh Chiu-Li, Yeh Sung-Ling

机构信息

School of Nutrition and Health Sciences, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.

Department of Surgery, Cathay General Hospital, Taipei, Taiwan.

出版信息

JPEN J Parenter Enteral Nutr. 2016 Nov;40(8):1122-1130. doi: 10.1177/0148607115587949. Epub 2015 Jun 9.

Abstract

BACKGROUND

This study investigated the effects of intravenous glutamine (GLN) administration on the expression of adhesion molecules and inflammatory mediators in a mice model of hind limb ischemia/reperfusion (IR) injury.

METHODS

There were 3 IR groups and 1 normal control (NC) group. The NC group did not undergo the IR procedure. Mice in the IR groups underwent 90 minutes of limb ischemia followed by a variable period of reperfusion. Ischemia was performed by applying a 4.5-oz orthodontic rubber band to the left thigh. Mice in one IR group were sacrificed immediately after reperfusion. The other 2 IR groups were injected once with either 0.75 g GLN/kg body weight (G group) or an equal volume of saline (S group) via tail vein before reperfusion. Mice in the S and G groups were subdivided and sacrificed at 4 or 24 hours after reperfusion.

RESULTS

IR enhanced the inflammatory cytokine gene expressions in muscle. Also, plasma interleukin (IL)-6 levels, blood neutrophil percentage, and the adhesion molecule and chemokine receptors expressed by leukocytes were upregulated after reperfusion. The IR-induced muscle inflammatory mediator gene expressions, blood macrophage percentage, and plasma IL-6 concentration had declined at an early or a late phase of reperfusion when GLN was administered. Histologic findings also found that remote lung injury was attenuated during IR insult.

CONCLUSIONS

A single dose of GLN administration immediately after sublethal lower limb ischemia reduces the inflammatory reaction locally and systemically; this may offer local and distant organ protection in hind limb IR injury.

摘要

背景

本研究在小鼠后肢缺血/再灌注(IR)损伤模型中,研究静脉注射谷氨酰胺(GLN)对黏附分子和炎症介质表达的影响。

方法

设置3个IR组和1个正常对照组(NC组)。NC组未进行IR操作。IR组小鼠经历90分钟的肢体缺血,随后进行不同时长的再灌注。通过在左大腿绑上一条4.5盎司的正畸橡皮筋来造成缺血。一个IR组的小鼠在再灌注后立即处死。另外2个IR组在再灌注前经尾静脉分别注射一次0.75 g GLN/ kg体重(G组)或等体积的生理盐水(S组)。S组和G组的小鼠再进一步细分,并在再灌注后4小时或24小时处死。

结果

IR增强了肌肉中炎性细胞因子基因的表达。此外,再灌注后血浆白细胞介素(IL)-6水平、血液中性粒细胞百分比以及白细胞表达的黏附分子和趋化因子受体均上调。给予GLN后,IR诱导的肌肉炎症介质基因表达、血液巨噬细胞百分比和血浆IL-6浓度在再灌注的早期或晚期有所下降。组织学结果还发现,在IR损伤期间,远处肺损伤得到减轻。

结论

在亚致死性下肢缺血后立即给予单剂量GLN可减轻局部和全身的炎症反应;这可能为后肢IR损伤提供局部和远处器官保护。

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