Department of Physiology, Ningxia Medical University, Yinchuan, Ningxia, P. R. China.
Endocrine Testing Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, P. R. China.
Spine (Phila Pa 1976). 2019 Jun 15;44(12):E715-E722. doi: 10.1097/BRS.0000000000002952.
A randomized, double-blind, controlled trial.
Few studies have investigated the changes in mitochondrial dynamics in spinal cord neurons. Meanwhile, the distribution of mitochondria in axons remains unclear. In the present study, the investigators attempted to clarify these questions and focused in observing the changes in mitochondrial spatial distribution under a high-glucose environment.
Mitochondrial dynamics disorder is one of the main mechanisms that lead to nervous system diseases due to its adverse effects on mitochondrial morphology, function, and axon distribution. High-glucose stress can promote the increase in mitochondrial fission of various types of cells.
The lumbar spinal cord of type 1 diabetic Sprague-Dawley rats at 4 weeks was observed. VSC4.1 cells were cultured and divided into three groups: normal control group, high-glucose intervention group, and high-glucose intervention combined with mitochondrial fission inhibitor Mdivi-1 intervention group. Immunohistochemistry and immunofluorescence methods were used to detect the expression of mitochondrial marker VDAC-1 in the spinal cord. An electron microscope was used to observe the number, structure, and distribution of mitochondria. Western blot was used to detect VDAC-1, fusion protein MFN1, MFN2, and OPA1, and fission protein FIS1 and DRP1. Living cell mitochondrial staining was performed using MitoTracker. Laser confocal microscopy and an Olympus live cell workstation were used to observe the mitochondrial changes.
The mitochondrial dynamics of spinal cord related neurons under an acute high-glucose environment were significantly unbalanced, including a reduction of fusion and increase of fission. Hence, mitochondrial fission has the absolute advantage. The total number of mitochondria in neuronal axons significantly decreased.
Increased mitochondrial fission and abnormal distribution occurred in spinal cord related neurons in a high-glucose environment. Mdivi-1 could significantly improve these disorders of mitochondria in VSC4.1 cells. Mitochondrial division inhibitors had a positive significance on diabetic neuropathy.
N/A.
随机、双盲、对照试验。
很少有研究调查过脊髓神经元中线粒体动力学的变化。同时，轴突中线粒体的分布尚不清楚。在本研究中，研究人员试图阐明这些问题，并专注于观察高糖环境下线粒体空间分布的变化。
线粒体动力学紊乱是导致神经系统疾病的主要机制之一，因为它对线粒体形态、功能和轴突分布有不良影响。高糖应激可促进各种类型细胞中线粒体裂变的增加。
观察 4 周 1 型糖尿病 Sprague-Dawley 大鼠的腰椎脊髓。培养 VSC4.1 细胞，并分为三组：正常对照组、高糖干预组和高糖干预联合线粒体裂变抑制剂 Mdivi-1 干预组。免疫组织化学和免疫荧光法检测脊髓中线粒体标志物 VDAC-1 的表达。电子显微镜观察线粒体的数量、结构和分布。Western blot 检测 VDAC-1、融合蛋白 MFN1、MFN2 和 OPA1 以及裂变蛋白 FIS1 和 DRP1。使用 MitoTracker 对活细胞线粒体进行染色。激光共聚焦显微镜和 Olympus 活细胞工作站观察线粒体变化。
急性高糖环境下脊髓相关神经元中线粒体动力学明显失衡，包括融合减少和裂变增加，因此线粒体裂变具有绝对优势。神经元轴突中线粒体的总数明显减少。
高糖环境下脊髓相关神经元中线粒体发生过度裂变和异常分布。Mdivi-1 可显著改善 VSC4.1 细胞中线粒体的这些异常。线粒体分裂抑制剂对糖尿病周围神经病变有积极意义。
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