Güçlü Aydın, Koçak Cengiz, Koçak Fatma E, Akçılar Raziye, Dodurga Yavuz, Akçılar Aydın, Elmas Levent
Department of Nephrology, Ahi Evran School of Medicine, Kırşehir, Turkey.
Department of Pathology, Dumlupınar School of Medicine, Kütahya, Turkey.
J Surg Res. 2017 Jan;207:241-248. doi: 10.1016/j.jss.2016.08.067. Epub 2016 Aug 27.
Acute renal failure is commonly seen in the perioperative period. Ischemia-reperfusion (IR) injury plays a major role in acute renal failure and delayed graft function. MicroRNAs (miRs), which are pivotal modulators of cell activities, offer a major opportunity for affective diagnosis and treatment strategies because they are tissue specific and in the center of gene expression modulation. The effect of bardoxolone methyl (BM) on miR-21, miR-223-5p, and miR-125b in renal IR injury was evaluated in this study.
Wistar-Albino rats (12-16 wk old, weighing 300-350 g) were used in the study. Rats (n = 6) were randomized into three groups (control, IR, and BM + IR). Tissue levels of miRs were analyzed with reverse transcription polymerase chain reaction.
Significant reduction of urea and total oxidant status, increase of total antioxidant status, and oxidative stress index were identified in the IR + BM group compared with the IR group. Significant increases of miR-21 (2842.82-fold) and miR-125b (536.8-fold) were identified in the IR group compared with the control group; however, miR-223-5p levels did not show any significant difference. Also, miR-21 and miR-125b were significantly reduced in the IR + BM group compared with the IR group. Reduced histopathologic changes were observed in the IR + BM group. A significant decrease in the number of tunel-positive cells was identified in the IR + BM group compared with the IR group.
miR-125b was significantly increased in IR injury; thus, miR-125b can be a potential novel marker that can be used in diagnosis and treatment of renal IR injury. BM reduces miR-21 and miR-125b in case of IR injury and makes functional and histopathologic repairs.
急性肾衰竭在围手术期较为常见。缺血再灌注（IR）损伤在急性肾衰竭和移植肾延迟复功中起主要作用。微小RNA（miRs）作为细胞活动的关键调节因子，因其具有组织特异性且处于基因表达调控的核心位置，为有效的诊断和治疗策略提供了重要契机。本研究评估了巴多昔芬甲酯（BM）对肾IR损伤中miR-21、miR-223-5p和miR-125b的影响。
本研究使用12 - 16周龄、体重300 - 350 g的Wistar白化大鼠。将大鼠（n = 6）随机分为三组（对照组、IR组和BM + IR组）。采用逆转录聚合酶链反应分析miRs的组织水平。
与IR组相比，IR + BM组的尿素和总氧化剂状态显著降低，总抗氧化状态和氧化应激指数升高。与对照组相比，IR组中miR-21（2842.82倍）和miR-125b（536.8倍）显著升高；然而，miR-223-5p水平未显示任何显著差异。此外，与IR组相比，IR + BM组中miR-21和miR-125b显著降低。IR + BM组的组织病理学变化减轻。与IR组相比，IR + BM组中TUNEL阳性细胞数量显著减少。
miR-125b在IR损伤中显著升高；因此，miR-125b可能是一种可用于肾IR损伤诊断和治疗的潜在新型标志物。在IR损伤时，BM可降低miR-21和miR-125b水平，并进行功能和组织病理学修复。
