中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (8): 1368-1374.doi: 10.4103/1673-5374.235249

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

晚期糖化产物升高小鼠氧化应激水平诱导发生神经管缺陷

  

  • 收稿日期:2018-01-06 出版日期:2018-08-15 发布日期:2018-08-15
  • 基金资助:

    陕西省技术委员会资助（2013JM4001）

Advanced glycation end products induce neural tube defects through elevating oxidative stress in mice

Ru-Lin Li, Wei-Wei Zhao, Bing-Yan Gao   

  1. Laboratory for Development, College of Life Sciences, Northwest University, Xi’an, Shaanxi Province, China
  • Received:2018-01-06 Online:2018-08-15 Published:2018-08-15
  • Contact: Ru-lin Li, M.D.,rulinli@nwu.edu.cn
  • Supported by:

    This study was supported by the grant from Shaanxi Technology Committee of China, No. 2013JM4001; and the China Scholarship Council (CSC).

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摘要：

为了解晚期糖化产物对神经管发育的影响及其分子机制，实验用含有3‰晚期糖化产物-牛血清白蛋白的商业饲料喂养C57BL6小鼠4周以诱导神经管缺陷，并用含3‰牛血清白蛋白的商业饲料喂养小鼠作对照。将小鼠进行交配，在妊娠第7.5天测定氧化应激标志物丙二醛和过氧化氢水平，并在妊娠第8.5天测定胚胎细胞的胞内活性氧水平。实验采用ELISA法测定妊娠第10.5天小鼠胚胎中胚胎蛋白对N-(羧甲基)赖氨酸抗体和羧乙基赖氨酸抗体的反应性并对神经管缺陷进行评价。结果显示，与对照小鼠相比，妊娠第10.5天，晚期糖化产物-牛血清白蛋白商业饲料喂养小鼠(未发生高血糖)神经管缺陷发生率明显增加，胚胎组织中胚胎蛋白对N-(羧甲基)赖氨酸和N(ε)-(羧乙基)赖氨酸抗体的反应性显著增加，妊娠第7.5天其胚胎组织中丙二醛和过氧化氢水平及妊娠第8.5天胚胎的细胞内活性氧水平明显升高，补充维生素E可部分逆转上述现象。结果表明，晚期糖化终产物-牛血清白蛋白能在不发生高血糖状态下可发生神经管缺陷，该机制至少部分与其在胚胎中氧化应激水平的增加有关。

orcid:0000-0003-0965-2518(Ru-Lin Li)

关键词: 神经管缺陷, 晚期糖化产物, 糖尿病胚胎综合症, 氧化应激, N-(羧甲基)赖氨酸, 丙二醛, (&epsilon, )-(羧乙基)赖氨酸, 胚胎, 过氧化氢, 牛血清白蛋白, 神经再生

Abstract:

Our previous study showed an association between advanced glycation end products (AGEs) and neural tube defects (NTDs). To understand the molecular mechanisms underlying the effect of AGEs on neural tube development, C57BL/6 female mice were fed for 4 weeks with commercial food containing 3% advanced glycation end product bovine serum albumin (AGE-BSA) or 3% bovine serum albumin (BSA) as a control. After mating mice, oxidative stress markers including malondialdehyde and H2O2 were measured at embryonic day 7.5 (E7.5) of gestation,and the level of intracellular reactive oxygen species (ROS) in embryonic cells was determined at E8.5. In addition to evaluating NTDs,an enzyme-linked immunosorbent assay was used to determine the effect of embryonic protein administration on the N-(carboxymethyl) lysine reactivity of acid and carboxyethyl lysine antibodies at E10.5. The results showed a remarkable increase in the incidence of NTDs at E10.5 in embryos of mice fed with AGE-BSA (no hyperglycemia) compared with control mice. Moreover, embryonic protein administration resulted in a noticeable increase in the reactivity of N-(carboxymethyl) lysine and N(ε)-(carboxyethyl) lysine antibodies. Malondialdehyde and H2O2 levels in embryonic cells were increased at E7.5, followed by increased intracellular ROS levels at E8.5. Vitamin E supplementation could partially recover these phenomena. Collectively, these results suggest that AGE-BSA could induce NTDs in the absence of hyperglycemia by an underlying mechanism that is at least partially associated with its capacity to increase embryonic oxidative stress levels.

Key words: nerve regeneration, neural tube defects, advanced glycation end products, diabetic embryopathy, oxidative stress, N-(carboxymethyl) lysine, malondiadehyde, N(ε)-(carboxyethyl) lysine, embryo, H2O2, bovine serum albumin, neural regeneration