Studies on the pathogenesis and treatment of diabetic neuropahy ; mechanisms of impaired regeneration of peripheral nerve and tiral for its inhibition

用光镜和电镜观察了链脲佐菌素（STZ）诱导的糖尿病大鼠周围神经离断后再生障碍。免疫细胞化学法检测神经生长因子受体（NFGR）的表达。为了进一步阐明受损再生的机制，还进行了神经丝（NF-68）mRNA水平的北方印迹分析。除了这些实验研究之外，还对人类活组织检查的腓肠神经样品进行了初步检查以确定NGFR的表达。糖尿病大鼠显示再生神经纤维的平均尺寸和轴突/纤维尺寸比显著减小，但在数量上没有显著差异，糖尿病大鼠和正常对照大鼠在神经切断后2- 4周实验期间再生的有髓神经纤维的密度。糖尿病大鼠NGFR的表达仅在切断神经后4周时降低。与正常对照组相比，糖尿病组NF-68 mRNA表达明显降低。再生障碍表现为有髓纤维变细，这可能与轴突神经丝合成减少有关。NGFR表达似乎与这种异常相关。人糖尿病神经与其他轴突型神经病变相似，显示NGFR的高表达。因此，NGFR-NF的合成似乎是糖尿病神经再生干扰的关键步骤。

Impaired regeneration of peripheral nerve was exmained in the severed peripheral nerve of streptozotocin (STZ)-induced diabetic rats with light and electron microscopic morphometrical analysis. Immunocytochemical evaluation on the expression of nerve growth factor receptor (NFGR) was also conducted. For the further elucidation of mechanisms of impaired regeneration, Northern blot analysis on mRNA levels of neurofilament (NF-68) was also performed. In addition to these experimental studies, preliminary examinations on the human biopsied sural nerve samples to determine the NGFR expression were also undertaken.Diabetic rats showed significant reduction of mean size of regenerated nerve fibers and axon/fiber size ratio, but there was no significant difference in the number, density of regenerated myelinated nerve fibers between diabetic and normal control rats during 2-4weeks experiments after nerve section. NGFR expression was reduced in diabetic rats only at the point of 4 weeks after the section of the nerve. NF-68 mRNA expression was significantly reduced in diabetic rats as compared with normal control rats. The impaired regeneration was represented by the thin myelinated fibers which are probably related to the reduced synthesis of axonal neurofilaments. NGFR expression appeared to correlate to this abnormality. Human diabetic nerves showed high expression of NGFR similar to other axonal type of neuropathy. Thus the NGFR-NF synthesis seems to be the crucial step for the perturbation of nerve regeneration in diabetes.