Hyperoside attenuates renal aging and injury induced by D-galactose via inhibiting AMPK-ULK1 signaling-mediated autophagy
Hyperoside attenuates renal aging and injury induced by D-galactose via inhibiting AMPK-ULK1 signaling-mediated autophagy
复制标题
金丝桃苷通过抑制 AMPK-ULK1 信号介导的自噬来减轻 D-半乳糖引起的肾脏衰老和损伤
DOI：
10.18632/aging.101723
复制
发表时间：
2018-12-01
期刊：
影响因子：
5.2
通讯作者：
Wan, Yigang
中科院分区：
文献类型：
--
作者：
Liu, Buhui;Tu, Yue;Wan, Yigang
肾脏是一个典型的经历年龄和损伤的器官。据报道金丝桃苷可用于预防由D-半乳糖（D-gal）诱导的衰老。然而，治疗机制仍不清楚。因此，我们旨在验证金丝桃苷与维生素E（VE）相比，是否可以通过调节自噬活性及其相关信号通路来减轻肾脏衰老和损伤。在体实验中，采用D-半乳糖诱导大鼠肾衰老模型，分别给予金丝桃苷和VE。分析肾脏衰老和损伤标志物、自噬活性和肾脏中AMPK-ULK 1信号通路的变化。在体外培养的NRK-52 E细胞中，采用组织形态计量学、免疫组化、免疫荧光、慢病毒转染和Western blot等方法，研究金丝桃苷和VE对细胞活力、肾小管细胞衰老标志物、自噬活性及其相关信号通路的调节作用。金丝桃苷和VE可减轻D-半乳糖所致的肾脏和肾小管细胞的衰老和损伤。金丝桃苷和VE通过mTOR非依赖性和AMPK-ULK 1信号通路抑制自噬活性。金丝桃苷作为一种类似VE的植物药成分，通过抑制AMPK-ULK 1介导的自噬，减轻D-半乳糖诱导的肾脏衰老和损伤。这项研究提供了金丝桃苷有助于预防年龄相关性肾损伤的第一个证据。
The kidney is a typical organ undergoing age and injury. Hyperoside is reported to be useful for preventing aging induced by D-galactose (D-gal). However, therapeutic mechanisms remain unclear. We thereby aimed to verify whether hyperoside, compared to vitamin E (VE), could alleviate renal aging and injury by regulating autophagic activity and its related signaling pathways. In vivo, rats were administered with either hyperoside or VE after renal aging modeling induced by D-gal. Changes in renal aging and injury markers, autophagic activity and AMPK-ULK1 signaling pathway in the kidneys were analysed. In vitro, the NRK-52E cells exposed to D-gal were used to investigate regulative actions of hyperoside and VE on cell viability, renal tubular cellular aging markers, autophagic activity and its related signaling pathways by histomorphometry, immunohistochemistry, immunofluorescence, lentiviral transfection and Western blot. Aging and injury in the kidneys and renal tubular cells induced by D-gal were ameliorated by hyperoside and VE. Hyperoside and VE inhibited autophagic activity through mTOR-independent and AMPK-ULK1 signaling pathways. Hyperoside, as a component of phytomedicine similar to VE, attenuated renal aging and injury induced by D-gal via inhibiting AMPK-ULK1-mediated autophagy. This study provides the first evidence that hyperoside contributes to the prevention of age-associated renal injury.