Yang Shikun, Han Yachun, Liu Jun, Song Panai, Xu Xiaoxuan, Zhao Li, Hu Chun, Xiao Li, Liu Fuyou, Zhang Hao, Sun Lin
Department of Nephrology, the Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011. China.
Department of Nephrology, the third Xiangya Hospital, Central South University, Changsha, Hunan 410011. China.
Curr Med Chem. 2017;24(29):3185-3202. doi: 10.2174/0929867324666170509121003.
Diabetic nephropathy (DN) is an important diabetic microvascular complication, and it is becoming the leading cause of end-stage renal disease worldwide. Unfortunately, there are no effective therapies to treat established DN. Therefore, new therapeutic targets are urgently required. Accumulating studies indicate that mitochondrial dysfunction is central to the pathogenesis of DN, and therapies targeted mitochondria might effectively delay the progression of DN.
A structured search of previously research literature about mitochondrial structure and function, mitochondrial DNA, mitochondrial biogenesis, mitochondrial dynamics change, mitophagy, mitochondrial ROS, mitochondrial apoptosis and therapies targeted mitochondria has been performed in several databases.
176 papers were included in this review, the results from these papers indicated that mitochondrial dysfunction is a pivotal issue for the development of DN, such as elevated oxidative stress induced by disorders of the mitochondrial respiratory chain complex and mitochondrial dynamic disorders, mutation of mitochondrial DNA, mitochondrial abnormal biogenesis, mitochondrial excessive fission, mitochondrial ROS overproduction. In addition, several therapeutic agents targeting the mitochondria (e.g mitochondrial ROS modulators, mitochondrial fragmentation inhibitors and mitochondrial biogenesis activators) have shown perfect therapeutic effect and security for DN.
The finding of this review has further confirmed the vital role of mitochondrial dysfunction in the progression of DN, management strategies for recovering the normal mitochondrial function will offer potential novel therapeutic targets for DN.
糖尿病肾病（DN）是一种重要的糖尿病微血管并发症，正成为全球终末期肾病的主要原因。不幸的是，目前尚无有效的疗法来治疗已确诊的DN。因此，迫切需要新的治疗靶点。越来越多的研究表明，线粒体功能障碍是DN发病机制的核心，针对线粒体的疗法可能有效延缓DN的进展。
在多个数据库中对先前有关线粒体结构与功能、线粒体DNA、线粒体生物发生、线粒体动力学变化、线粒体自噬、线粒体活性氧、线粒体凋亡以及针对线粒体的疗法的研究文献进行了结构化检索。
本综述纳入了176篇论文，这些论文的结果表明，线粒体功能障碍是DN发生发展的关键问题，如线粒体呼吸链复合物紊乱和线粒体动力学紊乱诱导的氧化应激升高、线粒体DNA突变、线粒体生物发生异常、线粒体过度分裂、线粒体活性氧过度产生。此外，几种针对线粒体的治疗药物（如线粒体活性氧调节剂、线粒体分裂抑制剂和线粒体生物发生激活剂）对DN显示出良好的治疗效果和安全性。
本综述的研究结果进一步证实了线粒体功能障碍在DN进展中的重要作用，恢复线粒体正常功能的管理策略将为DN提供潜在的新型治疗靶点。
