Creatine supplementation attenuates pulmonary and systemic effects of lung ischemia and reperfusion injury

Creatine supplementation attenuates pulmonary and systemic effects of lung ischemia and reperfusion injury
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DOI:
10.1016/j.healun.2015.06.012
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发表时间:
2016-02-01
影响因子:
8.9
通讯作者:
Vieira, Rodolfo Paula
Vieira, Rodolfo Paula
中科院分区:
医学1区
文献类型:
--
作者:
Almeida, Francine Maria;Oliveira-Junior, Manoel Carneiro;Vieira, Rodolfo Paula

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背景:肌酸是一种膳食补充剂,在心脏和脑缺血再灌注(I/R)损伤的实验模型中具有良好的作用。方法:40只雄性Wistar大鼠随机分为4组:假手术组、铬+假手术组、缺血/再灌注组和铬+缺血/再灌注组,观察左肺动脉缺血前(90分钟)和再灌流(120分钟)前5天补铬(0.5g/kg/d)对肺和全身反应的影响。中性粒细胞(p<0.001)和体循环中的中性粒细胞(p<0.001)。白介素1β(p<0.05)、组织阻尼和组织弹性(p<0.05)的水平也被降低。铬还抑制肺水肿的形成(p<0.001;组织学水肿指数,p<0.001)和肺组织中性粒细胞的聚集(p<0.001)。作为铬作用的可能机制,我们观察到caspase3的表达减少(p<0.001),Toll样受体4的表达减少(p<005),TLR7的表达增加(p<005)。这些有益的作用似乎与铬的抗炎和抗氧化特性以及对TLRs的调节有关。(C)2016年国际心肺移植学会。版权所有。
BACKGROUND: Creatine (Cr) is a dietary supplement that presents beneficial effects in experimental models of heart and brain ischemia and reperfusion (I/R) injury. It can improve adenosine 5'-triphosphate generation and reduce cell damage This study evaluated the effects of Cr supplementation in a model of lung PR.METHODS: Forty male Wistar rats were divided into 4 groups: sham operated, Cr+sham, I/R, and Cr+I/R. We investigated the effects of 5 days of Cr supplementation (0.5 g/kg/day by gavage) before left pulmonary artery ischemia (90 minutes) and reperfusion (120 minutes) on pulmonary and systemic response.RESULTS: Cr inhibited the I/R-induced increase in exhaled nitric oxide (p < 0.05), total cells (p < 0.01), and neutrophils (p < 0.001) in bronchoalveolar lavage fluid and in the systemic circulation (p < 0.001). The levels of interleulcin-1 beta (p < 0.05), tissue damping, and tissue elastance (p < 0.05) were also minimized Cr also inhibited pulmonary edema formation (total proteins in bronchoalveolar lavage fluid, p < 0.001; histologic edema index, p < 0.001) and neutrophils accumulation in lung tissue (p < 0.001). As possible mechanisms underlying Cr effects, we observed a reduced expression of caspase 3 (p < 0.05), reduced expression of Toll-like receptor (TLR) 4, and increased expression of TLR7 in lung tissue (p < 0.001).CONCLUSIONS: Cr supplementation presents pulmonary and systemic protective effects in acute lung injury induced by I/R in rats. These beneficial effects seem to be related to the anti-inflammatory and antioxidant properties of Cr and modulation of TLRs. (C) 2016 International Society for Heart and Lung Transplantation. All rights reserved.