Influence of mechanical ventilation and sepsis on redox balance in diaphragm, myocardium, limb muscles, and lungs

Influence of mechanical ventilation and sepsis on redox balance in diaphragm, myocardium, limb muscles, and lungs
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DOI:
10.1016/j.trsl.2014.07.003
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发表时间:
2014-12-01
影响因子:
7.8
通讯作者:
Barreiro, Esther
Barreiro, Esther
中科院分区:
医学2区
文献类型:
--
作者:
Chacon-Cabrera, Alba;Rojas, Yeny;Barreiro, Esther

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使用高潮气量(V-T)的机械通气(MV)会导致肺(呼吸机诱导的肺损伤(VILI))和远端器官损伤。此外,脓毒症的特征在于氧化应激增加。我们检测了MV是否与脓毒症(临床急性肺损伤中最常见的潜在疾病)中氧化应激增强相关。蛋白质羰基化和硝化、抗氧化剂和炎症(免疫印迹)在非脓毒症和脓毒症的膈肌、腓肠肌、比目鱼肌、心肌和肺中进行了评价。(在MV前24小时盲肠结扎和穿刺)进行MV的大鼠(每组n = 7),使用3种不同策略持续150分钟(低V-T(V-T = 9 mL/kg)、中度V-T(V-T = 15 mL/kg)和高V-T(V-T = 25 mL/kg))和非通气对照动物。与未通气的对照动物相比,在脓毒症和非脓毒症啮齿动物中,(1)高V-T大鼠的横膈膜、肢体肌肉和心肌显示出蛋白质氧化和硝化水平的降低,(2)抗氧化剂水平遵循慢肌和快肌中特定的纤维型分布,(3)肿瘤坏死因子α(TNF α)水平降低。(4)在肺中,蛋白质氧化增加,抗氧化剂相当减少,TNF-α保持不变。在该VILI模型中,在中度至高度V-T的MV数小时后,啮齿动物的远端器官或骨骼肌中未发生氧化应激,而动物肺中的蛋白质氧化水平增加。炎症事件在MV大鼠的骨骼肌和肺中中度表达。伴随脓毒症不会强烈影响MV对啮齿动物肌肉、心肌或肺的诱导作用。
Mechanical ventilation (MV), using high tidal volumes (V-T), causes lung (ventilator-induced lung injury (VILI)) and distant organ injury. Additionally, sepsis is characterized by increased oxidative stress. We tested whether MV is associated with enhanced oxidative stress in sepsis, the commonest underlying condition in clinical acute lung injury. Protein carbonylation and nitration, antioxidants, and inflammation (immunoblotting) were evaluated in diaphragm, gastrocnemius, soleus, myocardium, and lungs of nonseptic and septic (cecal ligation and puncture 24 hours before MV) rats undergoing MV (n = 7 per group) for 150 minutes using 3 different strategies (low V-T (V-T = 9 mL/kg), moderate V-T (V-T = 15 mL/kg), and high V-T (V-T = 25 mL/kg)) and in nonventilated control animals. Compared with nonventilated control animals, in septic and nonseptic rodents (1) diaphragms, limb muscles, and myocardium of high-V-T rats exhibited a decrease in protein oxidation and nitration levels, (2) antioxidant levels followed a specific fiber-type distribution in slow- and fast-twitch muscles, (3) tumor necrosis factor alpha (TNF-alpha) levels were higher in respiratory and limb muscles, whereas no differences were observed in myocardium, and (4) in lungs, protein oxidation was increased, antioxidants were rather decreased, and TNF-alpha remained unmodified. In this model of VILI, oxidative stress does not occur in distant organs or skeletal muscles of rodents after several hours of MV with moderate-to-high V-T, whereas protein oxidation levels were increased in the lungs of the animals. Inflammatory events were moderately expressed in skeletal muscles and lungs of the MV rats. Concomitant sepsis did not strongly affect the MV-induced effects on muscles, myocardium, or lungs in the rodents.