Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
Arch Med Res. 2009 Oct;40(7):536-44. doi: 10.1016/j.arcmed.2009.09.005.
The aim of this study was to investigate the GLP-1 pathway effect on peripheral nerves using a DPP-IV inhibitor in streptozotocin (STZ)-induced diabetic rats.
Adult male Sprague Dawley rats were divided into four groups and two groups (n=6 in each) were given a DPP-IV inhibitor of 0.3mg/kg/day or 10mg/kg/day dissolved in water. Intraepidermal innervation was quantified as nerve fiber abundance per unit length of epidermis (IENF/mm) following an immunohistochemical procedure using the polyclonal antibody of anti-protein gene product 9.5 (PGP 9.5).
Daily administration of DPP-IV inhibitor to the experimental diabetes model at doses of 10mg/kg for 32 weeks protected nerve fiber loss compared with untreated rats as follows (IENF/mm): normal (9.89+/-0.34), diabetes mellitus (DM) (8.42+/-0.28), DM with 0.3mg/kg DPP-IV inhibitor (9.88+/-0.38), and DM with 10mg/kg DPP-IV inhibitor (10.36+/-0.32) (p<0.05). There was a significant reduction (% change) in the decrease of intraepidermal nerve fiber density (IENFD) in the DPP-IV inhibitor-treated groups during the experimental period: normal (10.1%), DM (25.8%), DM with 0.3mg/kg DPP-IV inhibitor (13.3%), and DM with 10mg/kg DPP-IV inhibitor (7.9%) (p<0.05).
Our study suggests that a DPP-IV inhibitor may prevent peripheral nerve degeneration in a diabetes-induced animal model and support the idea that GLP-1 may be useful in peripheral neuropathy.
本研究旨在通过二肽基肽酶-4（DPP-4）抑制剂在链脲佐菌素（STZ）诱导的糖尿病大鼠中研究 GLP-1 通路对周围神经的影响。
成年雄性 Sprague Dawley 大鼠分为四组，两组（每组 6 只）分别给予每日 0.3mg/kg 或 10mg/kg 的 DPP-4 抑制剂溶解于水中。通过使用多克隆抗蛋白基因产物 9.5（PGP 9.5）抗体的免疫组织化学程序，定量表皮内神经纤维密度作为单位长度表皮中的神经纤维丰度（IENF/mm）。
每日给予实验性糖尿病模型 10mg/kg 的 DPP-4 抑制剂治疗 32 周可保护神经纤维丢失，与未治疗大鼠相比如下（IENF/mm）：正常（9.89+/-0.34）、糖尿病（DM）（8.42+/-0.28）、DM 用 0.3mg/kg DPP-4 抑制剂（9.88+/-0.38）和 DM 用 10mg/kg DPP-4 抑制剂（10.36+/-0.32）（p<0.05）。在实验期间，DPP-4 抑制剂治疗组的表皮内神经纤维密度（IENFD）下降幅度显著降低（%变化）：正常（10.1%）、DM（25.8%）、DM 用 0.3mg/kg DPP-4 抑制剂（13.3%）和 DM 用 10mg/kg DPP-4 抑制剂（7.9%）（p<0.05）。
我们的研究表明，DPP-4 抑制剂可能预防糖尿病诱导的动物模型中的周围神经变性，并支持 GLP-1 可能对周围神经病变有用的观点。
