藏药灰兜巴调节线粒体动力学平衡减轻糖尿病肾病足细胞损伤分子机制研究

Recent research has shown that,mitochondrial dynamics plays an important role in T2DM and its vascular complications.Oxidative stress of mitochondria induced by continuous high glucose environment can trigger excessive fission of mitochondria and lead to mitochondrial dynamics imbalance.Previous study of the research group found that the medicine of nourishing qi and nourishing yin Tibetan medicine Huidouba could significantly reduce proteinuria and kidney injury in DN rats, and down-regulate the expression level of NOX4 in kidney，which is the main generating system of mitochondrial ROS.Based on this, we propose a hypothesis that Huidouba can regulate the mitochondria dynamic balance by reducing oxidative stress in DN high glucose environment，and then alleviate the damage and apoptosis of podocytes in DN.In this paper,from a new perspective of mitochondrial dynamic balance, we will discuss by what mechanism Huidouba alleviates the damage and apoptosis of podocytes and then slows down the development of DN, which will provide a scientific basis for the treatment of DN with Tibetan medicine.

新近研究表明，线粒体动力学平衡在T2DM及其血管并发症中起着至关重要作用。持续高糖环境诱发的线粒体氧化应激可触发线粒体过度分裂，导致线粒体动力学失衡。课题组前期研究发现，益气养阴藏药灰兜巴可明显降低DN大鼠蛋白尿，减轻肾脏损伤，并下调肾脏NOX4表达水平，而NOX4是线粒体ROS主要生成系统。基于此，我们提出假说：灰兜巴通过减轻DN高糖环境所诱发的氧化应激，从而调控线粒体动力学平衡，减轻足细胞损伤及凋亡，发挥DN保护作用。本课题将以自发性DN动物模型db/db小鼠为研究对象，以益气养阴藏药灰兜巴为研究载体，聚焦于DN足细胞损伤及修复变化，采用激光扫描共聚焦显微镜、免疫荧光双标法、PCR芯片技术、Western Blot、RT-PCR等检测技术，从线粒体动力学平衡新视角，探讨灰兜巴减轻足细胞损伤及凋亡从而缓解DN发生发展的分子机制，为藏药灰兜巴治疗DN提供科学依据。

新近研究表明，线粒体动力学平衡在T2DM及其血管并发症中起着至关重要作用。持续高糖环境诱发的线粒体氧化应激可触发线粒体过度分裂，导致线粒体动力学失衡。课题组前期研究发现，益气养阴藏药灰兜巴可明显降低DN大鼠蛋白尿，减轻肾脏损伤，并下调肾脏NOX4表达水平，而NOX4是线粒体ROS主要生成系统。基于此，课题组提出假说：灰兜巴通过减轻DN高糖环境所诱发的氧化应激，从而调控线粒体动力学平衡，减轻足细胞损伤及凋亡，发挥DN保护作用。该项目以自发性DN动物模型db/db小鼠为研究对象，以益气养阴藏药灰兜巴为研究载体，聚焦于DN足细胞损伤及修复变化，采用激光扫描共聚焦显微镜、免疫荧光双标法、PCR芯片技术、Western Blot、RT-PCR等检测技术，从线粒体动力学平衡新视角，明确了灰兜巴减轻足细胞损伤，降低蛋白尿，延缓DN发生发展的治疗作用，并从动物、组织、细胞、分子四个层次，深入挖掘了灰兜巴调控线粒体动力学平衡，减轻足细胞氧化应激损伤，治疗DN的分子机制，为民间药灰兜巴治疗DN提供实验依据，并拓展了靶向线粒体治疗DN的新思路。