ERK磷酸化对糖尿病周围神经病雪旺氏细胞Netrin-1表达水平及凋亡的影响  

The effects of ERK pathway on Schwann cell apoptosis and Netrin-1 expression level in diabetic peripheral neuropathy

作　　者：李林 徐长水 张平[1] 张清贵[1] 刘北彦 Li Ling;Xu Changshui;Zhang Ping(Department of Neurology,the First Affiliated Hospital of Xinxiang Medical University,Xinxiang Henan 453100)

机构地区：[1]河南省新乡医学院第一附属医院神经内科,453100 [2]河南省新乡医学院第一附属医院内分泌科,453100

出　　处：《卒中与神经疾病》2020年第4期430-434,共5页Stroke and Nervous Diseases

摘　　要：目的探讨ERK通路对糖尿病周围神经病雪旺氏细胞凋亡以及Netrin-1表达水平的影响。方法建立动物和细胞模型分析ERK通路对雪旺氏细胞以及Netrin-1表达水平的影响。结果观察糖尿病模型小鼠坐骨神经组织中p-ERK的表达增加,ERK抑制剂PD98059抑制高糖诱导雪旺氏细胞中ERK的磷酸化,即ERK通路促进糖尿病周围神经疾病的发生;糖尿病模型小鼠坐骨神经组织中Netrin-1表达减少,ERK抑制剂PD98059增加高糖刺激中雪旺氏细胞中Netrin-1的表达,即ERK抑制剂通过增加Netrin-1的表达来发挥神经保护作用;PD98059可逆转高糖诱导雪旺氏细胞中Caspase-3的表达和细胞凋亡,即ERK抑制剂降低雪旺氏细胞凋亡,从而防止糖尿病周围神经疾病的发展。结论 ERK抑制剂可抑制糖尿病周围神经疾病雪旺氏细胞的凋亡以及增加Nertin-1的表达,从而发挥保护作用。Objective To investigate the effects of ERK pathway on Schwann apoptosis and Netrin-1 expression level in diabetic peripheral neuropathy. Methods Animal and cell models were established to analyze the effects of ERK pathway on Schwann cell apoptosis and Netrin-1 expression level. Results The increased expression level of p-ERK in sciatic nerve tissue of diabetic mice was observed. PD98059, a ERK inhibitor, inhibited the phosphorylation of ERK induced by high glucose in Schwann cells. The results showed that ERK pathway promoted the occurrence of diabetic peripheral nerve disease. The expression level of Netrin-1 decreased in the sciatic nerve tissue of diabetic mice, PD98059 increased the expression level of Netrin-1 stimulated by high glucose in Schwann cells, which indicated that ERK inhibitors played a neuroprotective role by increasing the Netrin-1 expression level. PD98059 could reverse the expression level of Caspase-3 and Schwann cell apoptosis induced by high glucose, which indicated that ERK inhibitors reduced Schwann cell apoptosis and prevented the development of peripheral nerve disease. Conclusion ERK inhibitor could inhibit Schwann cell apoptosis and increase the Netrin-1 expression level, and play a neuroprotective role in diabetic peripheral neuropathy.

关 键 词：糖尿病周围神经病变 雪旺氏细胞 ERK 

分 类 号：R745.49[医药卫生—神经病学与精神病学]