Activation of Sirtuin 3 by Silybin Attenuates Mitochondrial Dysfunction in Cisplatin-induced Acute Kidney Injury.
Activation of Sirtuin 3 by Silybin Attenuates Mitochondrial Dysfunction in Cisplatin-induced Acute Kidney Injury.
复制标题
水飞蓟宾激活 Sirtuin 3 可减轻顺铂诱导的急性肾损伤中的线粒体功能障碍
DOI：
10.3389/fphar.2017.00178
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发表时间：
2017
影响因子：
5.6
通讯作者：
Lou T
中科院分区：
文献类型：
--
作者：
Li Y;Ye Z;Lai W;Rao J;Huang W;Zhang X;Yao Z;Lou T
水飞蓟宾是从水飞蓟种子中分离得到的一种次级代谢产物，具有抗炎、抗氧化、抗纤维化和抗肿瘤的特性。在这里，我们发现，水飞蓟宾通过调节sirtuin 3（SIRT3）表达改善线粒体功能，从而保护顺铂诱导的急性肾损伤（阿基）。向雄性SV129和SIRT3敲除（KO）小鼠施用单次腹膜内（i.p.）注射顺铂，用或不用水飞蓟宾治疗。此外，培养的HK 2细胞用于评估线粒体形态和功能。我们的数据表明，水飞蓟宾增强SIRT3表达后，顺铂管理在体内和体外。水飞蓟宾治疗改善了野生型细胞和小鼠的线粒体功能和生物能量学，但对SIRT3缺陷细胞和小鼠没有改善。此外，我们证明，水飞蓟宾显着衰减顺铂诱导的阿基和肾小管细胞凋亡，并改善SIRT3依赖的方式细胞再生。总的来说，这些结果表明，水飞蓟宾是SIRT3的药理学激活剂，能够通过改善线粒体功能来防止顺铂诱导的肾小管细胞凋亡和阿基。因此，水飞蓟宾可作为一种潜在的临床肾保护辅助治疗顺铂化疗。
Silybin is a secondary metabolite isolated from the seeds of blessed milk thistle (Silybum marianum) that has anti-inflammatory, antioxidative, antifibrotic, and antitumor properties. Here, we showed that silybin protected against cisplatin-induced acute kidney injury (AKI) by improving mitochondrial function through the regulation of sirtuin 3 (SIRT3) expression. Male SV129 and SIRT3 knockout (KO) mice were administered a single intraperitoneal (i.p.) injection of cisplatin with or without treatment with silybin. Moreover, cultured HK2 cells were used to evaluate mitochondrial morphology and function. Our data suggested that silybin enhanced SIRT3 expression after cisplatin administration both in vivo and in vitro. Silybin treatment improved mitochondrial function and bioenergetics in wild-type, but not SIRT3-defective, cells and mice. Moreover, we demonstrated that silybin markedly attenuated cisplatin-induced AKI and tubular cell apoptosis and improved cell regeneration in a SIRT3-dependent manner. Collectively, these results suggest that silybin is a pharmacological activator of SIRT3 capable of protecting against cisplatin-induced tubular cell apoptosis and AKI by improving mitochondrial function. Thus, silybin could serve as a potential clinical renoprotective adjuvant treatment in cisplatin chemotherapy.