The effect of levosimendan on lung damage after myocardial ischemia reperfusion in rats in which experimental diabetes was induced
The effect of levosimendan on lung damage after myocardial ischemia reperfusion in rats in which experimental diabetes was induced
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DOI：
10.1016/j.jss.2014.08.038
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发表时间：
2015-02-01
影响因子：
2.2
通讯作者：
Kavutcu, Mustafa
中科院分区：
文献类型：
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作者：
Alkan, Metin;Celik, Ali;Kavutcu, Mustafa
背景：众所周知，糖尿病并发症与脂质过氧化反应密切相关。在缺血和再灌注（IR）期间，损伤可能发生在远处器官以及暴露于缺血的区域附近的组织中，并且肺可能是这些器官中受影响最严重的器官之一。因此，本研究探讨了左西孟旦对肺组织和氧化-抗氧化系统在糖尿病rates.Materials和方法：这项研究进行了24 Wistar白化病大鼠，分为四组（C，对照; DC，糖尿病对照; DRILL，糖尿病IR;和DIRL，糖尿病IR左西孟旦）。用链脲佐菌素（55 mg/kg）在18只大鼠中诱发糖尿病，在糖尿病的影响变得明显后，将动物随机分为三组。左胸切口后，左冠状动脉主干（LAD）心肌缺血30 min。DIRL组于缺血前腹腔注射左西孟旦12 mg/kg。DC组作为糖尿病对照组，C组6只大鼠作为对照组，开胸后关胸，不诱导心肌缺血。我们测量了脂质过氧化终产物丙二醛的水平，以及过氧化氢酶和谷胱甘肽S-转移酶的活性，作为肺组织中的抗氧化酶。结果：与C组、DC组和DIRL组相比，BALF组肺组织中的神经细胞浸润或聚集明显增多（P = 0.003、P = 0.026和P = 0.026）。与C、DC和DIRL组相比，BALF组的肺组织肺泡壁增厚显著更高（分别为P = 0.002、P = 0.002和P = 0.006）。此外，与C、DC和DIRL组相比，BALF组的肺组织损伤评分显著更高（分别为P = 0.001、P = 0.004和P = 0.007）。最后，过氧化氢酶和谷胱甘肽S-转移酶的活性水平显着较高，与观察到的C，DC，和DIRL groups.Conclusions：虽然糖尿病增加脂质过氧化作用，它抑制抗氧化活性在RISK组。我们的研究结果表明，左西孟旦对诱导糖尿病大鼠IR继发性肺损伤具有保护作用。我们建议进行实验和临床研究，以检查不同剂量和不同IR持续时间的左西孟旦对各种器官的影响，以供临床使用。(C)2015 Elsevier Inc. All rights reserved.
Background: It is known that diabetic complications and lipid peroxidation are closely associated. During ischemia and reperfusion (IR), injury may occur in distant organs, as well as in tissues next to the region exposed to the ischemia, and the lungs can be one of the most affected of these organs. Therefore, this study investigated the effects of levosimendan on lung tissue and the oxidant-antioxidant system in diabetic rats.Materials and methods: The study was conducted in 24 Wistar albino rats that were separated into four groups (C, control; DC, diabetic control; DIR, diabetic IR; and DIRL, diabetic IR levosimendan). Diabetes was induced in 18 rats using streptozotocin (55 mg/kg), and the animals were randomly separated into three groups after the effects of the diabetes became apparent. After a left thoracotomy, ischemia was performed on the myocardial muscle with the left main coronary artery (LAD) for 30 min in the DIR and DIRL groups. After ischemia, the LAD ligation was removed, and reperfusion was applied for 120 min. Single-dose intraperitoneal 12 mg/kg levosimendan was administered to group DIRL before the ischemia. Group DC was evaluated as the diabetic control group, and six rats were considered to be the control group (group C), in which thoracotomy was performed and then closed with no induction of myocardial ischemia. We measured the levels of malondialdehyde, as a lipid peroxidation end product, as well as catalase and glutathione S-transferase activities, as antioxidant enzymes in the lung tissue. Tissue samples were also examined histopathologically.Results: Neutrophil infiltration or aggregation in lung tissue was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.003, P = 0.026, and P = 0.026, respectively). Alveolar wall thickening in lung tissue was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.002, P = 0.002, and P = 0.006, respectively). In addition, the lung tissue damage score was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.001, P = 0.004, and P = 0.007, respectively). Finally, catalase and glutathione S-transferase activity levels were significantly higher in the DIR group compared with those observed in the C, DC, and DIRL groups.Conclusions: Although diabetes increases lipid peroxidation, it suppresses antioxidant activity. Our results showed that levosimendan had a protective effect against lung damage secondary to IR in the rats with induced diabetes. We recommend that experimental and clinical studies be conducted to examine the effects of levosimendan at different doses and different IR durations on various organs for clinical use. (C) 2015 Elsevier Inc. All rights reserved.