文章摘要
星型胶质细胞和小胶质细胞在1型糖尿病小鼠外周神经病变中的作用
Effect of astrocytes and microglia in peripheral neuropathy of type 1 diabetic mice
  
DOI：10.12089/jca.2020.11.015
中文关键词: 糖尿病  外周神经病变  星型胶质细胞  小胶质细胞  脂肪酸结合蛋白7
英文关键词: Diabetes  Peripheral neuropathy  Astrocytes  Microglia  Fatty acid-binging protein 7
基金项目:江苏省研究生科研与实践创新计划项目（KYCX18_1503）
作者单位E-mail
简娇敏 201600,上海市,南京医科大学上海松江临床医学院麻醉科  
纪健 201600,上海市,南京医科大学上海松江临床医学院麻醉科  
陈冲 201600,上海市,南京医科大学上海松江临床医学院麻醉科  
娄晓丽 201600,上海市,南京医科大学上海松江临床医学院中心实验室  
朱涛 201600,上海市,南京医科大学上海松江临床医学院麻醉科 zt19192003@163.com 
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中文摘要:
      
目的 观察星形胶质细胞和小胶质细胞标志物在1型糖尿病外周神经病变小鼠脊髓中的表达变化。
方法 SPF级健康雄性C57BL/6小鼠30只，6周龄，体重18~22 g，采用随机数字表法分为两组：对照组（C组）和糖尿病组（DM组）。DM组采用链脲佐菌素（STZ）（100 mg/kg，连续2 d腹腔注射）制备1型糖尿病小鼠模型，C组给予同等剂量柠檬酸钠缓冲液连续2 d。记录两组小鼠造模前、造模后1、2、4、6、8、10周的体重、随机血糖、机械缩足反应阈（MWT）、热缩足潜伏期（TWL）。生化检测分别选取C组和DM组1周、10周的脊髓。采用Western blot法测定L4—L6脊髓脂肪酸结合蛋白7（FABP7）、星形胶质细胞特异性标记物胶质纤维酸性蛋白（GFAP）、小胶质细胞标记物（CD11b、iba1）表达量，Elisa法测定小鼠脊髓组织中肿瘤坏死因子α（TNF-α）、IL-10浓度，免疫组化法测定足底表皮神经纤维密度（IENFD）。
结果 与C组比较，DM组造模后2、4、6、8、10周体重、MWT明显降低（P＜0.05或P＜0.01），造模后1、2、4、6、8、10周血糖明显升高（P＜0.01），造模后4、6、8、10周TWL明显延长（P＜0.05或P＜0.01）；造模后1周FABP7和GFAP表达量明显升高（P＜0.05）；造模后10周FABP7、CD11b、iba1表达量明显升高（P＜0.05）；造模后10周脊髓组织中IL-10、TNF-α浓度明显升高（P＜0.05）；造模后10周IENFD明显降低（P＜0.05）。
结论 糖尿病模型小鼠造模后1周脊髓中星形胶质细胞活化但小胶质细胞无明显改变，而造模后10周星形胶质细胞已恢复正常但小胶质细胞活化，1型糖尿病外周神经病变中星型胶质细胞较小胶质细胞更早的激活。
英文摘要:
      
Ojective To observe the expression of astrocyte and microglia biomarkers in the spinal cord of mice with type 1 diabetic peripheral neuropathy.
Methods Thirty SPF-grade healthy male C57BL/6 mice, 6 weeks old, weighing 18-22 g, were divided into 2 groups by random number table method: control group (group C) and diabetes mellitus group (group DM). Mice in group DM was treated with streptozotocin (STZ) (100 mg/kg,intraperitoneally injected for 2 consecutive days) to make type 1 diabetic mice model, and the mice in group C were given the same dose of sodium citrate buffer for 2 consecutive days. The weight, blood glucose, mechanical withdrawal threshold (MWT) and thermal withdrawal latency(TWL) of mice in both groups were recorded before modeling and 1, 2, 4, 6, 8, and 10 weeks after modeling. The L4-6 spinal cords of mice in group C and group DM 1 week and 10 weeks after modeling were taken for biochemical detection. The expressions of fatty acid-binding protein7(FABP7), astrocyte biomarker glial fibrillary acidic protein(GFAP), and microglia biomarker(CD11b and iba1) were detected by Western blot method. The levels of TNF-α and IL-10 were detected by enzyme-linked immunosorbent assay. Plantar intraepidermal nerve fiber density (IENFD) was detected by immunohistochemical method.
Results Compared with group C, the weight and MWT in group DM significantly decreased 2, 4, 6, 8, 10 weeks after modeling (P < 0.05 or P < 0.01), the blood glucose significantly increased of group DM 1, 2, 4, 6, 8, 10 weeks after modeling (P < 0.01), and the TWL of group DM obviously extended 4, 6, 8, 10 weeks after modeling (P < 0.05 or P < 0.01). The expressions of FABP7 and GFAP were elevated (P < 0.05) 1 week after modeling, the expressions of FABP7, CD11b, iba1 and the concentration of TNF-α and IL-10 within spinal cord tissues were significantly elevated in 10 weeks (P < 0.05). However, the IENFD was reduced in 10 weeks after modeling.
Conclusion The astrocytes in the spinal cord of the diabetic mice were active but the microglia did not change significantly 1 week after the modeling, and the astrocytes had returned to normal but the microglia were active in 10 weeks after the modeling. The outcomes indicate that in type 1 diabetic peripheral neuropathy, astrocytes are active earlier than microglia.
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