Sirtuin 3 缺乏加重对比剂诱导的急性肾损伤。
Sirtuin 3 deficiency aggravates contrast-induced acute kidney injury.
机构信息
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.
Intensive Care Unit, Weifang People's Hospital, Weifang, Shandong, China.
出版信息
J Transl Med. 2018 Nov 16;16(1):313. doi: 10.1186/s12967-018-1690-5.
BACKGROUND
Sirtuin 3 (Sirt3) is a key regulator of energy metabolism and oxidative stress. To investigate the role of Sirt3 in contrast-induced acute kidney injury (CIAKI), we established the model both in vivo and in vitro to explore the potential mechanisms.
METHODS
In vivo, we established CIAKI models in wild-type (WT) and Sirt3-knockout (Sirt3-KO) mice. Blood urea nitrogen (BUN) and serum creatinine (Scr) were detected by enzyme-linked immunosorbent assay, Glomerular Filtration Rate (GFR) and creatinine clearance were also investigated. We detected the production of reactive oxygen species (ROS) via 2'7'-dichlorodihydro-fluorescein diacetate. The expressions of Sirt3, oxidative stress and apoptosis related markers (MnSOD, Catalase, Acetyl-MnSOD K68, Nox4, Bax, Bcl-2 and Caspase3) were measured and analyzed. In addition, we observed the effect of nicotinamide riboside (NR) on CIAKI in WT and Sirt3-KO mice. In vitro, Sirt3 was knocked out by siRNA transfection method in HK-2 cells. Sirt3, ROS, oxidative stress and apoptosis markers in HK-2 cells were also measured.
RESULTS
Our data demonstrated that the levels of Scr and BUN in Sirt3-KO mice were increased while the levels of the GFR and creatinine clearance were decreased in CIAKI mice. In Sirt3-KO or siRNA groups, the activities of MnSOD and Catalase were markedly down-regulated. Also, the expression of Caspase3 were markedly increased and the ratio of Bcl-2/Bax was decreased, while the ROS level was increased in Sirt3 deficiency groups. NR ameliorated CIAKI in WT mice but not in Sirt3-KO mice.
CONCLUSION
Our results suggest that Sirt3 deficiency aggravates contrast-induced acute kidney injury. Sirt3 is critical in NR-mediated renoprotection in CIAKI.
背景
Sirtuin 3（Sirt3）是能量代谢和氧化应激的关键调节因子。为了研究 Sirt3 在对比诱导的急性肾损伤（CIAKI）中的作用，我们在体内和体外建立了模型，以探讨潜在的机制。
方法
在体内，我们在野生型（WT）和 Sirt3 敲除（Sirt3-KO）小鼠中建立 CIAKI 模型。通过酶联免疫吸附试验检测血尿素氮（BUN）和血清肌酐（Scr），还研究了肾小球滤过率（GFR）和肌酐清除率。通过 2'7'-二氯二氢荧光素二乙酸酯检测活性氧（ROS）的产生。测量和分析 Sirt3、氧化应激和凋亡相关标志物（MnSOD、Catalase、乙酰化-MnSOD K68、Nox4、Bax、Bcl-2 和 Caspase3）的表达。此外，我们观察了烟酰胺核糖（NR）对 WT 和 Sirt3-KO 小鼠 CIAKI 的影响。在体外，通过 siRNA 转染方法敲除 HK-2 细胞中的 Sirt3。还测量和分析了 HK-2 细胞中的 Sirt3、ROS、氧化应激和凋亡标志物。
结果
我们的数据表明，在 CIAKI 小鼠中，Sirt3-KO 小鼠的 Scr 和 BUN 水平升高，而 GFR 和肌酐清除率降低。在 Sirt3-KO 或 siRNA 组中，MnSOD 和 Catalase 的活性明显下调。此外，Caspase3 的表达明显增加，Bcl-2/Bax 的比值降低，而 Sirt3 缺乏组的 ROS 水平升高。NR 改善了 WT 小鼠的 CIAKI，但对 Sirt3-KO 小鼠没有改善。
结论
我们的结果表明，Sirt3 缺乏加重了对比诱导的急性肾损伤。Sirt3 在 NR 介导的 CIAKI 肾保护中至关重要。
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