Resveratrol ameliorates disorders of mitochondrial biogenesis and dynamics in a rat chronic ocular hypertension model
Resveratrol ameliorates disorders of mitochondrial biogenesis and dynamics in a rat chronic ocular hypertension model
复制标题
白藜芦醇可改善大鼠慢性高眼压模型中线粒体生物发生和动力学的紊乱。
DOI：
10.1016/j.lfs.2018.06.010
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发表时间：
2018-08-15
期刊：
影响因子：
6.1
通讯作者：
Yuan, Fei
中科院分区：
文献类型：
--
作者：
Zhang, Xi;Feng, Yifan;Yuan, Fei
目的：探讨线粒体生物发生和动力学在高压诱导的RGC-5细胞凋亡和大鼠视网膜损伤中的作用及其在白藜芦醇(RSV)诱导的细胞保护中的作用。材料与方法：采用前房注射超顺磁性氧化铁的方法建立大鼠慢性高眼压模型。RGC-5细胞分别在常压和加压(70 Mm Hg)下孵育。用手持式Tonolab眼压计测量眼压(IOP)，用膜电位去极化(MMPs)、活性氧(ROS)水平和透射电子显微镜(TEM)检测分析线粒体功能障碍。Annexin V/PI染色和末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)染色检测细胞凋亡。苏木精-伊红染色检测视网膜形态。免疫印迹分析线粒体生物发生和动力学相关蛋白的表达。主要发现：慢性高眼压(COH)大鼠视网膜形态和线粒体功能恶化。在加压(70 Mm Hg)孵育条件下，细胞出现凋亡和线粒体功能障碍。在体内外实验中，RSV上调AMPK、NRF-1、Tfam、MFN-2、OPA1的表达，可减少细胞凋亡、线粒体膜电位去极化、ROS的产生，并使体内视网膜形态正常化。
Aims: To explore the roles of mitochondrial biogenesis and dynamics in both RGC-5 cells apoptosis and rat retinal damage induced by elevated pressure and their involvement in resveratrol (RSV)-induced cell protection.Materials and methods: The chronic ocular hypertension (COH) model was established in rats by injecting superparamagnetic iron oxide into anterior chamber. The RGC-5 cells were incubated under ambient and elevated pressure (70 mm Hg) respectively. The intraocular pressure (IOP) was measured using a handheld Tonolab tonometer; mitochondrial dysfunction was analyzed by membrane potential (MMP) depolarization, reactive oxygen species (ROS) level and transmission electron microscope (TEM) detection. Annexin V/PI staining and the terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining assay were performed for apoptosis detection. Hematoxylin-Eosin staining was performed for retinal morphology detection. The expression of mitochondrial biogenesis and dynamics relating proteins were analyzed by western blot.Key findings: The retinal morphology and mitochondrial function deteriorated in chronic ocular hypertension (COH) rats. The cells showed apoptosis and mitochondrial dysfunction under elevated pressure (70mmHg) incubation. Upregulating AMPK, NRF-1, Tfam, mfn-2, OPA1 expression with RSV-treatment could decrease the cell apoptosis, mitochondrial membrane potential depolarization, ROS generation both in in vitro and in vivo experiments, and normalized the retinal morphology in vivo.