Curcumin Attenuates Renal Ischemia and Reperfusion Injury-Induced Restrictive Respiratory Insufficiency
Curcumin Attenuates Renal Ischemia and Reperfusion Injury-Induced Restrictive Respiratory Insufficiency
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DOI：
10.1016/j.transproceed.2013.09.004
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发表时间：
2013-12-01
影响因子：
0.9
通讯作者：
Wang, J. -J.
中科院分区：
文献类型：
--
作者：
Yeh, J. -H.;Yang, Y. -C.;Wang, J. -J.
Objective.肺衰竭而不是肾衰竭是急性肾损伤（阿基）相关死亡的主要原因之一。容量超负荷以前被认为是肺损伤的主要原因，可能是肾液清除受损。最近的证据表明，在阿基期间释放的促炎细胞因子、趋化因子和自由基在肺损伤中起着至关重要的作用。我们的目的是研究姜黄素预处理对肺功能的保护作用。通过45分钟的肾缺血（双侧肾蒂闭塞）随后3小时的再灌注来诱导阿基。将大鼠分为假手术组、肾缺血再灌注组（I/R）和I/R前口服姜黄素（12.5mg/kg/d）2d组。在基线和再灌注3小时后进行肺功能测试（PFT），产生肺容积、弦顺应性（Cchord）、吸气阻力（RI）和前200毫秒用力呼气量（FEV 200）的参数。我们还检测了支气管肺泡灌洗液（BAL）中蛋白浓度（PC）、甲基胍（MG）、肿瘤坏死因子-α（TNF-α）和丙二醛（MDA）的水平。缺血性AKI诱导的限制性肺病表现为Cchord、总肺容量（TLC）和FEV 200降低，以及灌洗液PCBAL、MG、TNF-α和MDA水平升高。姜黄素预处理可改善肺功能损害和肺泡血管蛋白漏出，减轻肺部炎症。姜黄素预处理对限制性肺病的保护作用最可能与减少肺中的羟基自由基、脂质过氧化和炎症以及改善肺泡血管通透性有关。
Objective. Pulmonary failure, instead of kidney failure, is one of the leading causes of acute kidney injury (AKI)-related death. Volume overload was previously regarded as the primary cause of lung injury, presumably by impaired renal fluid clearance. Recent evidence suggested that proinflammatory cytokines, chemokines, and free radicals released during AKI are playing a crucial role in the lung injury. We aimed to examine the protective efficacy of lung function with curcumin pretreatment.Methods. AKI was induced by 45 minutes of kidney ischemia (bilateral occlusion of renal pedicles) followed by 3 hours of reperfusion. Rats were divided into 3 groups: sham-operated, kidney ischemia and reperfusion (I/R), and a group with 2 days of oral pretreatment with curcumin (12.5 mg/kg/d) before I/R injury. The pulmonary function test (PFT) was conducted at baseline and after 3 hours of reperfusion, yielding parameters of lung volumes, chord compliance (Cchord), inspiratory resistance (RI), and forced expiratory volume at the first 200 millisecond (FEV200). We also examined levels of protein concentration (PC), methylguanidine (MG), tumor necrosis factor-alpha (TNF-alpha), and malondialdehyde (MDA) in the bronchoalveolar lavage (BAL).Results. Ischemic AKI-induced restrictive lung disease was demonstrated by the decreased Cchord, total lung capacitance (TLC), and FEV200, in addition to the increased lavage PCBAL, MG, TNF-alpha, and MDA level. Curcumin pretreatment ameliorated lung function impairment and alveolar vascular protein leak and attenuated lung inflammation.Conclusions. The protective effect of curcumin pretreatment against restrictive lung disease is most likely associated with decreasing hydroxyl radical, lipid peroxidation, and inflammation in the lungs and improving alveolar vascular permeability.