Protective Effect of Melatonin on Infrarenal Aortic Occlusion: This Effect Is Related to Anti-inflammatory Effect and Antioxidant Effect
Protective Effect of Melatonin on Infrarenal Aortic Occlusion: This Effect Is Related to Anti-inflammatory Effect and Antioxidant Effect
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DOI：
10.1007/s10753-014-9835-z
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发表时间：
2014-08-01
期刊：
影响因子：
5.1
通讯作者：
Yuksel, Seref
中科院分区：
文献类型：
--
作者：
Ahsen, Ahmet;Gonul, Yucel;Yuksel, Seref
在腹主动脉（AA）手术期间经常施加主动脉交叉夹闭。在AA手术中观察到的缺血再灌注（IR）损伤是一种复杂的情况，不仅在下肢，而且在远端组织和器官（如肺、肾、心脏和肝脏）中也被考虑[1-6]。IR损伤由于其全身性并发症而导致重要的发病率和死亡率[7，8]。急性肾功能不全是AA择期手术后最重要的并发症之一，仍然是常见的疾病（15-22%），但急性肾损伤（阿基）相对罕见（1.8-4%）[9，10]。已证明主动脉的双肾夹闭会减少肾血流量，尤其是在术后发生肾衰竭的患者中[11-13]。该钳夹程序可通过在肾动脉水平的主动脉中形成湍流而引起肾动脉中的血管收缩[13]。IR诱导的器官损伤的潜在机制可能是多因素和相互依赖的，涉及缺氧、炎症反应和自由基损伤[14-17]。IR损伤的病理生理学中的两个最重要的因素是活性氧（ROS）和全身炎症介质的大量分泌，其尤其在再灌注阶段增加[18-20]。在再灌注期间负责保护免受ROS的内源性抗氧化剂在减少IR损伤中具有重要作用[18]。褪黑激素是松果体产生的主要吲哚胺，已被证明是一种有效的抗氧化剂和自由基清除剂[21-24]。此外，它还显示出抗炎作用，即抑制促炎细胞因子，如肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和IL-6 [25-30]。褪黑激素具有小尺寸和高亲脂性;因此，它很容易穿过生物膜并到达细胞的所有部分[22，31，32]。在这项研究中，我们的目的是调查的抗炎，抗氧化和保护作用的褪黑激素在肾下主动脉闭塞-再灌注大鼠模型的肾脏IR损伤的发展，并防止这种损害。
Aortic cross-clamping is frequently exerted during surgery of the abdominal aorta (AA). Ischemia–reperfusion (IR) damage, which is observed in the surgery of AA, is a complex situation and is considered not only in lower extremities but also in remote tissues and organs like the lungs, kidneys, heart, and liver [1–6]. IR damage leads to important morbidity and mortality because of its systemic complications [7, 8]. Acute renal dysfunction, which is one of the most important complications following elective surgery of AA, is still a frequently seen condition (15–22%), but acute kidney injury (AKI) is relatively rare (1.8–4%)[9, 10]. Infrarenal clamping of the aorta has been shown to decrease renal blood flow especially in patients who postoperatively developed renal failure [11–13]. This clamping procedure can cause vasoconstriction in renal arteries by forming turbulent flow in the aorta at the level of renal arteries [13].The mechanisms underlying IR-induced organ damage are likely multifactorial and interdependent, involving hypoxia, inflammatory responses, and free radical damage [14–17]. Two of the most important factors in the pathophysiology of IR injury are reactive oxygen species (ROS) and massive secretion of systemic inflammatory mediators, which especially increase in the reperfusion phase [18–20]. The endogenous antioxidants which are responsible for protecting against ROS during reperfusion have an important role in decreasing IR injury [18]. Melatonin, the main indolamine produced by the pineal gland, has been demonstrated to be an effective antioxidant and free radical scavenger [21–24]. Additionally, it has also shown an anti-inflammatory effect, which is suppression of proinflammatory cytokines like tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 [25–30]. Melatonin has a small size and high lipophilicity; therefore, it crosses biological membranes easily and reaches all sections of the cell [22, 31, 32]. In this study, we aimed to investigate the anti-inflammatory, antioxidant, and protective effects of melatonin in IR damage developing in kidneys following infrarenal aortic occlusion–reperfusion in rat models and in preventing kidneys from this kind of damage.