From the Departments of Medical Science.
Physiology.
Plast Reconstr Surg. 2023 Feb 1;151(2):355-364. doi: 10.1097/PRS.0000000000009844. Epub 2022 Nov 11.
The relationship between autophagy and diabetic peripheral neuropathy (DPN) has been highlighted in few reports. Using an animal model, the authors investigated the relationship between autophagy and DPN, focused particularly on changes in autophagy in Schwann cells.
The ultrastructural features of DPN mice were evaluated in vivo using transmission electron microscopy. Dysfunction of autophagy in DPN was evaluated using immunofluorescence microscopy and Western blot analysis of proteins related to autophagy, including Beclin1, LC3, and p62. Reactive oxygen species levels were measured in vitro in glucose-treated Schwann cells. Dysfunction of autophagy in glucose-treated Schwann cells was examined by immunofluorescence microscopy and Western blot analysis.
Reduced myelin thickness and axonal shrinkage were observed in the sciatic nerves of DPN mice. Reactive oxygen species levels were increased in Schwann cells treated with high glucose ( P < 0.05). The expression of Beclin1 was increased in DPN mice and Schwann cells treated with high glucose ( P < 0.05), whereas the expression of LC3-II/LC3-I ratio and p62 were decreased in DPN mice and Schwann cells treated with high glucose ( P < 0.05).
These results suggest that increased levels of reactive oxygen species induced by high glucose may contribute to autophagy dysfunction in Schwann cells. Autophagy dysfunction especially in Schwann cells may be an underlying cause of DPN.
This study presents the pathological mechanism of diabetic peripheral neuropathy.
自噬与糖尿病周围神经病变（DPN）之间的关系已在少数报道中得到强调。作者使用动物模型研究了自噬与 DPN 之间的关系，特别关注施万细胞中自噬的变化。
通过透射电子显微镜在体内评估 DPN 小鼠的超微结构特征。使用免疫荧光显微镜和与自噬相关的蛋白质（包括 Beclin1、LC3 和 p62）的 Western blot 分析评估 DPN 中的自噬功能障碍。在体外葡萄糖处理的施万细胞中测量活性氧（ROS）水平。通过免疫荧光显微镜和 Western blot 分析检查葡萄糖处理的施万细胞中的自噬功能障碍。
DPN 小鼠坐骨神经中观察到髓鞘厚度减少和轴突收缩。高葡萄糖处理的施万细胞中 ROS 水平升高（P<0.05）。Beclin1 在 DPN 小鼠和高葡萄糖处理的施万细胞中的表达增加（P<0.05），而 LC3-II/LC3-I 比值和 p62 在 DPN 小鼠和高葡萄糖处理的施万细胞中的表达降低（P<0.05）。
这些结果表明，高葡萄糖诱导的活性氧水平升高可能导致施万细胞自噬功能障碍。自噬功能障碍，特别是施万细胞中的自噬功能障碍，可能是 DPN 的潜在原因。
本研究提出了糖尿病周围神经病变的病理机制。
