The effects of IL-18BP on mRNA expression of inflammatory cytokines and apoptotic genes in renal injury induced by infrarenal aortic occlusion

The effects of IL-18BP on mRNA expression of inflammatory cytokines and apoptotic genes in renal injury induced by infrarenal aortic occlusion
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DOI:
10.1016/j.jss.2015.12.026
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发表时间:
2016-05-01
影响因子:
2.2
通讯作者:
Songur, Ahmet
Songur, Ahmet
中科院分区:
医学3区
文献类型:
--
作者:
Gonul, Yucel;Genc, Abdurrahman;Songur, Ahmet

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背景:肾损伤是肾下主动脉闭塞(IAO)的重要并发症,主要发生在术后期间。主动脉夹闭手术可能会导致血流紊流,并最终导致腹主动脉肾动脉水平的血管收缩。 IL-18BP 具有众所周知的抗氧化和抗炎特性。本研究旨在探讨IL-18BP对IAO大鼠模型引起的急性肾损伤是否具有抗炎、抗凋亡、抗氧化和保护作用。 材料与方法:将30只成年雄性Wistar-Albino大鼠均匀随机分为三组:SHAM剖腹手术组、缺血再灌注(IR)组和IR+IL-18BP组。我们应用 30 分钟 IAO 和 2 小时再灌注。测量炎症细胞因子水平(TNF-α、IL-1β、IL-18、IL-6 和 IFN-γ)和氧化应激参数(TAS、TOS 和 OSI)。除此之外,还研究了尿素和肌酐水平、肾脏组织病理学、炎性细胞因子的mRNA表达水平和凋亡基因。结果:与IR组相比,IR + IL-18BP组的尿素和肌酐、组织和血清中TNF-α、IL-6、IL-18、IFN-γ和TOS的水平以及氧化应激指数(OSI)显着降低。组织病理学检查显示,IR+IL-18BP预处理组炎性细胞因子和凋亡基因mRNA表达水平显着降低,IR组与其他三组比较差异有统计学意义(P < 0.001)。这些改善通过组织病理学损伤的总分得到证明。在我们之前的研究中,我们已经证明IL-18BP对肝脏和脊髓IR损伤具有抗氧化、抗炎和保护作用。本研究建立的数据表明,IL-18BP可能对IAO诱导的大鼠急性肾损伤发挥抗炎、抗凋亡、抗氧化和保护作用,这将是该领域的首次研究。结论:本研究建立的数据表明,IL-18BP可能对IAO诱导的大鼠急性肾损伤发挥抗炎、抗凋亡、抗氧化和保护作用。 (C) 2016 Elsevier Inc. 保留所有权利。
Background: Renal injury is an important complication of infrarenal aortic occlusion (IAO), which is mainly encountered during the postoperative period. Aortic clamping procedure may lead to turbulent blood flow and eventually vasoconstriction at renal arterial level of the abdominal aorta. IL-18BP has well-known antioxidant and anti-inflammatory properties. In this study, we aimed to determine whether IL-18BP has anti-inflammatory, antiapoptotic, antioxidant, and protective effects on acute kidney damage induced by IAO rat model.Materials and methods: A total of 30 adult male Wistar-Albino rats were equally and randomly separated to three groups as follows: SHAM laparotomy, ischemia-reperfusion (IR), and IR + IL-18BP. We applied 30-min IAO and 2-h reperfusion. Inflammatory cytokine levels (TNF-alpha, IL-1 beta, IL-18, IL-6, and IFN-gamma) and oxidative stress parameters (TAS, TOS, and OSI) were measured. In addition to this, urea and creatinine levels, histopathology of kidney, mRNA expression levels of inflammatory cytokines, and apoptotic genes were investigated.Results: Urea and creatinine, tissue and serum levels of TNF-alpha, IL-6, IL-18, IFN-gamma, and TOS, and oxidative stress index (OSI) were found significantly lower in IR + IL-18BP group, when compared to the IR group. Moreover, mRNA expression levels of inflammatory cytokines and apoptotic genes were prominently depressed in IR + IL-18BP pre-treatment group in histopathologic examination, there was a significant difference between the IR and other three groups (P < 0.001). These improvements were demonstrated with a total score of histopathologic damage. In our previous studies, we have demonstrated that IL-18BP has antioxidant, inflammatory, and protective effects on liver and spinal cord IR injury. Data established from the present study suggest that IL-18BP may exert anti-inflammatory, antiapoptotic, antioxidant, and protective effects on IAO-induced acute kidney injury in rats, and this would be the first study to be conducted in this field.Conclusions: Data established from the present study suggest that IL-18BP may exert anti-inflammatory, antiapoptotic, antioxidant, and protective effects on IAO-induced acute kidney injury in rats. (C) 2016 Elsevier Inc. All rights reserved.