Tu Yiji, Chen Zenggan, Hu Junda, Ding Zuoyou, Lineaweaver William C, Dellon A Lee, Zhang Feng
Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, China.
Joseph M. Still Burn and Reconstructive Center, Jackson, Mississippi.
J Reconstr Microsurg. 2018 Sep;34(7):537-548. doi: 10.1055/s-0038-1642023. Epub 2018 Apr 25.
This article investigates the role of chronic nerve compression in the progression of diabetic peripheral neuropathy (DPN) by gene expression profiling.
Chronic nerve compression was created in streptozotocin (STZ)-induced diabetic rats by wrapping a silicone tube around the sciatic nerve (SCN). Neurological deficits were evaluated using pain threshold test, motor nerve conduction velocity (MNCV), and histopathologic examination. Differentially expressed genes (DGEs) and metabolic processes associated with chronic nerve compression were analyzed.
Significant changes in withdrawal threshold and MNCV were observed in diabetic rats 6 weeks after diabetes induction, and in DPN rats 4 weeks after diabetes induction. Histopathologic examination of the SCN in DPN rats presented typical changes of myelin degeneration in DPN. Function analyses of DEGs demonstrated that biological processes related to inflammatory response, extracellular matrix component, and synaptic transmission were upregulated after diabetes induction, and chronic nerve compression further enhanced those changes. While processes related to lipid and glucose metabolism, response to insulin, and apoptosis regulation were inhibited after diabetes induction, chronic nerve compression further enhanced these inhibitions.
Our study suggests that additional silicone tube wrapping on the SCN of rat with diabetes closely mimics the course and pathologic findings of human DPN. Further studies are needed to verify the effectiveness of this rat model of DPN and elucidate the roles of the individual genes in the progression of DPN.
本文通过基因表达谱分析研究慢性神经压迫在糖尿病周围神经病变（DPN）进展中的作用。
通过在坐骨神经（SCN）周围包裹硅胶管，在链脲佐菌素（STZ）诱导的糖尿病大鼠中造成慢性神经压迫。使用疼痛阈值测试、运动神经传导速度（MNCV）和组织病理学检查评估神经功能缺损。分析与慢性神经压迫相关的差异表达基因（DGE）和代谢过程。
在糖尿病诱导后6周的糖尿病大鼠以及糖尿病诱导后4周的DPN大鼠中，观察到撤药阈值和MNCV有显著变化。DPN大鼠SCN的组织病理学检查呈现出DPN中典型的髓鞘变性变化。对DEG的功能分析表明，与炎症反应、细胞外基质成分和突触传递相关的生物学过程在糖尿病诱导后上调，而慢性神经压迫进一步增强了这些变化。虽然与脂质和葡萄糖代谢、胰岛素反应及细胞凋亡调节相关的过程在糖尿病诱导后受到抑制，但慢性神经压迫进一步增强了这些抑制作用。
我们的研究表明，在糖尿病大鼠的SCN上额外包裹硅胶管可密切模拟人类DPN的病程和病理表现。需要进一步研究来验证这种DPN大鼠模型的有效性，并阐明各个基因在DPN进展中的作用。
