Abstract
Objective This article investigates the role of chronic nerve compression in the progression
of diabetic peripheral neuropathy (DPN) by gene expression profiling.
Methods 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.
Results 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.
Conclusion 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.
Keywords
diabetes - peripheral neuropathy - DNA microarray
