中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (3): 513-518.doi: 10.4103/1673-5374.245590

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

丁基苯酞干预可减轻高糖诱导许旺细胞的损伤：与抑制细胞硝基化及细胞凋亡有关？

  

  • 出版日期:2019-03-15 发布日期:2019-03-15
  • 基金资助:

    安徽省自然科学基金资助(1608085MH209)；中国科学技术大学新医学项目(WK 110000036)

3-N-Butylphthalide mitigates high glucose-induced injury to Schwann cells: association with nitrosation and apoptosis

Dan-Dan Xu 1, 2 , Wen-Ting Li 3 , Dan Jiang 2 , Huai-Guo Wu 2 , Ming-Shan Ren 1 , Mei-Qiao Chen 4 , Yuan-Bo Wu 1   

  1. 1 Department of Neurology, First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui Province, China
    2 Department of Neurology, Anhui Second People’s Hospital, Hefei, Anhui Province, China
    3 Department of Infection, First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui Province, China
    4 Department of Neurology, Affiliated Anhui Provincial Hospital of Anhui Medical University, Hefei, Anhui Province, China
  • Online:2019-03-15 Published:2019-03-15
  • Contact: Yuan-Bo Wu, PhD, sky627@163.com.
  • Supported by:

     This study was supported by the Natural Science Foundation of Anhui Province, China, No. 1608085MH209 (to YBW); New Medicine of University of Science and Techology of China, No. WK110000036 (to YBW).

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摘要：

高糖状态易造成周围神经轴突萎缩、脱髓鞘、神经纤维功能丧失及再生延缓等神经损伤，但在糖尿病周围神经病变中硝基化是否也会有关键性作用研究较少。为此，实验拟探讨高糖环境下形成周围神经髓鞘对许旺细胞经丁基苯酞处理后，其细胞增殖、凋亡和3-硝基酪氨酸蛋白表达的变化，并初步揭示丁基苯酞的对周围神经的保护机制。(1)采用高浓度葡萄糖(100 mM)体外培养大鼠许旺细胞(Boster Biological Technology, Wuhan, China)，采用过氧亚硝基抑制剂尿酸1 μM及丁基苯肽10 M处理48 h，应用CCK8及流式细胞技术观察尿酸及丁基苯肽对高糖培养许旺细胞增殖及细胞凋亡的影响。运用ELISA法检测尿酸及丁基苯肽对许旺细胞内3-硝基酪氨酸蛋白表达的影响；(2)结果显示，高糖培养许旺细胞增殖活性降低，细胞凋亡及胞内3-硝基酪氨酸蛋白表达增加；而尿酸及丁基苯肽干预能够增加高糖培养许旺细胞的增殖活性，抑制细胞凋亡及胞内3-硝基酪氨酸蛋白表达；(3)由此可见，丁基苯肽可能具有抑制细胞硝基化及细胞凋亡，并促进细胞增殖的作用，以此减轻高浓度葡萄糖对许旺细胞的损伤。

orcid: 0000-0003-2661-744X(Yuan-Bo Wu)
           0000-0002-6749-2412(Dan-Dan Xu)

关键词: 许旺细胞, 3-N-丁基苯酞, 3-NT, 3-硝基酪氨酸, 硝化应激, 尿酸, ONOO-, 糖尿病周围神经病变, 凋亡, 增殖, 神经再生

Abstract:

A high glucose state readily causes peripheral axon atrophy, demyelination, loss of nerve fiber function, and delayed regeneration. However, few studies have examined whether nitration is also critical for diabetic peripheral neuropathy. Therefore, this study investigated the effects of high glucose on proliferation, apoptosis, and 3-nitrotyrosine levels of Schwann cells treated with butylphthalide. In addition, we explored potential protective mechanisms of butylphthalide on peripheral nerves. Schwann cells were cultured in vitro with high glucose then stim¬ulated with the peroxynitrite anion inhibitors uric acid and 3-n-butylphthalide for 48 hours. Cell Counting Kit-8 and flow cytometry were used to investigate the effects of uric acid and 3-n-butylphthalide on proliferation and apoptosis of Schwann cells exposed to a high glucose environment. Effects of uric acid and 3-n-butylphthalide on levels of 3-nitrotyrosine in Schwann cells were detected by enzyme-linked im¬munosorbent assay. The results indicated that Schwann cells cultured in high glucose showed decreased proliferation, but increased apoptosis and intracellular 3-nitrotyrosine levels. However, intervention with uric acid or 3-n-butylphthalide could increase proliferation of Schwann cells cultured in high glucose, and inhibited apoptosis and intracellular 3-nitrotyrosine levels. According to our data, 3-n-butylphthalide may inhibit cell nitrification and apoptosis, and promote cell proliferation, thereby reducing damage to Schwann cells caused by high glucose.

Key words: nerve regeneration, Schwann cells, 3-n-butylphthalide, 3-nitrotyrosine, nitration stress, uric acid, peroxynitrite anions, diabetic peripheral neuropathy, apoptosis, proliferation, neural regeneration