摘要
背景:糖尿病肾病(DN)是一种重要的糖尿病性微血管并发症,已成为全球终末期肾病的主要原因。不幸的是,没有有效的治疗方法来治疗已建立的DN。因此,迫切需要新的治疗靶点。累积研究表明,线粒体功能障碍是DN的发病机制的核心,靶向线粒体的疗法可能有效延缓DN的进展。 方法:已经在几个数据库中进行了关于线粒体结构和功能,线粒体DNA,线粒体生物发生,线粒体动力学变化,线粒体线粒体ROS,线粒体凋亡和靶向线粒体疗法的先前研究文献的结构化搜索。 结果:本研究纳入176篇论文,结果表明线粒体功能障碍是DN发展的关键问题,如线粒体呼吸链复合物和线粒体动力障碍病变引起的氧化应激升高,突变线粒体DNA,线粒体异常生物发生,线粒体过度裂变,线粒体ROS过度产生。此外,靶向线粒体的几种治疗剂(例如线粒体ROS调节剂,线粒体碎裂抑制剂和线粒体生物发生激活剂)已经显示出DN的完美治疗效果和安全性。 结论:本次回顾的发现进一步证实了线粒体功能障碍在DN进展中的重要作用,恢复正常线粒体功能的治疗策略将为DN提供潜在的新型治疗靶点。背景:糖尿病肾病(DN)是一种重要的糖尿病性微血管并发症,已成为全球终末期肾病的主要原因。不幸的是,没有有效的治疗方法来治疗已建立的DN。因此,迫切需要新的治疗靶点。累积研究表明,线粒体功能障碍是DN的发病机制的核心,靶向线粒体的疗法可能有效延缓DN的进展。 方法:已经在几个数据库中进行了关于线粒体结构和功能,线粒体DNA,线粒体生物发生,线粒体动力学变化,线粒体线粒体ROS,线粒体凋亡和靶向线粒体疗法的先前研究文献的结构化搜索。 结果:本研究纳入176篇论文,结果表明线粒体功能障碍是DN发展的关键问题,如线粒体呼吸链复合物和线粒体动力障碍病变引起的氧化应激升高,突变线粒体DNA,线粒体异常生物发生,线粒体过度裂变,线粒体ROS过度产生。此外,靶向线粒体的几种治疗剂(例如线粒体ROS调节剂,线粒体碎裂抑制剂和线粒体生物发生激活剂)已经显示出DN的完美治疗效果和安全性。 结论:本次回顾的发现进一步证实了线粒体功能障碍在DN进展中的重要作用,恢复正常线粒体功能的治疗策略将为DN提供潜在的新型治疗靶点。
关键词: 线粒体,肾损伤,糖尿病肾病,微血管并发症,线粒体功能障碍,线粒体。
Current Medicinal Chemistry
Title:Mitochondria: A Novel Therapeutic Target in Diabetic Nephropathy
Volume: 24 Issue: 29
关键词: 线粒体,肾损伤,糖尿病肾病,微血管并发症,线粒体功能障碍,线粒体。
摘要: Background: 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.
Method: 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.
Result: 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.
Conclusion: 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.
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Cite this article as:
Mitochondria: A Novel Therapeutic Target in Diabetic Nephropathy, Current Medicinal Chemistry 2017; 24 (29) . https://dx.doi.org/10.2174/0929867324666170509121003
DOI https://dx.doi.org/10.2174/0929867324666170509121003 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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