【糖尿病.DPN.2018】胰岛素葡萄糖控制与α硫辛酸（ALA）对链脲佐菌素（STZ）诱导的糖尿病大鼠周围神经保护方面的比较

文献DOI：10.1007/s12020-018-1613-5

文献PMID：29736880

文献原文链接：http://doi.org.sci-hub.tw/10.1007/s12020-018-1613-5

Comparison of peripheral nerve protection between insulin-based glucose control and alpha lipoic acid (ALA) in the streptozotocin (STZ)-induced diabetic rat

胰岛素葡萄糖控制与α硫辛酸（ALA）对链脲佐菌素（STZ）诱导的糖尿病大鼠周围神经保护方面的比较

【Abstract】

Strict glucose control is a well-proven therapeutic approach for peripheral neuropathies in patients with diabetes. Alpha lipoic acid (ALA) has also been accepted as a therapeutic agent for diabetic peripheral neuropathy (DPN) in the respect of pathogenesis. However, the potential of ALA as a treatment for DPN in comparison to that of glucose control is unclear. In this study, we compared the neuroprotective potential of glucose control and ALA. Animals were divided into 6 groups based on the intervention used, as follows: normal, diabetes (DM), DM+racemic form of ALA, DM+R form of ALA, DM +once daily insulin glargine, and DM+once daily insulin glargine with twice daily insulin glulisine. Various sensory tests were performed after 12 weeks of treatment, and immunohistochemistry of nerve fibers obtained from the sciatic and cutaneous nerves was performed after 24 weeks of treatment. There were no significant differences between the ALA-treated and insulin-treated DM groups in the sensory tests or in antioxidant activity. The axonal diameters and myelin sheath area of the sciatic nerves and the cutaneous small nerves, as assessed based on intraepidermal nerve fiber density, were similar in the ALA-treated and insulin-treated animals, although there was a non-significant trend for a mild increase in the both basal and rapid-acting insulin group compared with non-treated DM group. In conclusion, our results suggest that the neuroprotective benefits of ALA and insulin-based glucose control may be similar, although glucose control may have had slightly more beneficial effects in this animal model of diabetes. Of note, glucose levels should be strictly controlled, including corrections for fluctuations in the glucose level, to obtain therapeutic benefits in DPN.

Keywords Alpha lipoic acid ● Diabetes ● Glucose control ● Peripheral neuropathy

摘要翻译：

严格的血糖控制是糖尿病患者外周神经病变的一种久经考验的治疗方法。在发病机理方面，α-硫辛酸（ALA）也被认为是糖尿病周围神经病变（DPN）的治疗剂。然而，与葡萄糖控制相比，ALA作为DPN治疗的潜力尚未完全清楚。在这项研究中，我们比较了葡萄糖控制和ALA的神经保护潜力。根据使用干预措施将动物分为6组，如下：正常组，糖尿病（DM）组，DM +外消旋形式的ALA组，DM + R形式的ALA组，DM +每日一次甘精胰岛素组和DM +每日一次甘精胰岛素每日服用两次谷赖胰岛素组。在治疗12周后进行各种感觉测试，并且在治疗24周后进行从坐骨神经和皮神经获得的神经纤维的免疫组织化学。在感觉测试或抗氧化活性中，ALA处理的和胰岛素处理的DM组之间没有显著差异。基于表皮内神经纤维密度评估的坐骨神经和皮肤小神经的轴突直径和髓鞘面积在ALA治疗和胰岛素治疗的动物中相似。尽管与未治疗的DM组相比，基础和速效胰岛素组均有轻微增加的非显著趋势。总之，我们的结果表明ALA和基于胰岛素的葡萄糖控制的神经保护作用可能是相似的，尽管在这种糖尿病动物模型中葡萄糖控制可能具有略微更有益的作用。值得注意的是，应严格控制葡萄糖水平，包括校正葡萄糖水平的波动，以获得DPN的治疗益处。

关键词α-硫辛酸●糖尿病●葡萄糖控制●周围神经病变