中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (6): 938-943.doi: 10.4103/1673-5374.158357

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

丙烯酰胺对断乳期大脑的神经毒性

  

  • 收稿日期:2015-05-12 出版日期:2015-06-18 发布日期:2015-06-18
  • 基金资助:

    广东省医学科研基金资助（b2014202）和广东省自然科学基金（2014a030310455）

Acrylamide neurotoxicity on the cerebrum of weaning rats

Su-min Tian 1, Yu-xin Ma 1, Jing Shi 2, Ting-ye Lou 3, Shuai-shuai Liu 4, Guo-ying Li 1   

  1. 1 School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China
    2 Xiqiao People’s Hospital, Foshan, Guangdong Province, China
    3 Clinical Laboratory of First Affiliated Hospital, Xinxiang Medical University, Xinxiang, Henan Province, China
    4 Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
  • Received:2015-05-12 Online:2015-06-18 Published:2015-06-18
  • Contact: Guo-ying Li, M.D., Ph.D., gzlgying820@sina.com.
  • Supported by:

     This study was supported by the Medical Scientific Research Foundation of Guangdong Province in China, No. B2014202; and the Natural Science Foundation of Guangdong Province in China, No. 2014A030310455.

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摘要：

丙烯酰胺的神经毒性的机制存在争议。以往的研究主要集中在丙烯酰胺对成人和啮齿类动物的影响，对断乳期大鼠丙烯酰胺的神经毒性的研究较少。为进一步探讨丙烯酰胺对发育期大脑的毒性作用及机制，实验用断乳期幼年大鼠建立丙烯酰胺(5，15，30 mg/kg) 构建每周5次，连续灌胃4周亚急性染毒的动物模型。神经功能检测显示：丙烯酰胺5 mg/kg亚急性染毒幼年大鼠未出现明显的神经功能受损症状，而丙烯酰胺15，30 mg/kg则可引起大鼠明显的步态异常。大脑生化指标检测显示，15，30 mg/kg组大鼠大脑皮质内谷氨酸含量显著性降低，γ-氨基丁酸的含量则显著性升高，且都呈剂量-效应关系；免疫组织化学染色显示，15，30 mg/kg丙烯酰胺组大鼠大脑皮质内神经元细胞发生变性损伤；大脑皮质内γ-氨基丁酸、γ-氨基丁酸能神经元标记物谷氨酸脱羧酶及胶质纤维酸性蛋白的表达均显著增加。结果证实丙烯酰胺对断乳期幼年大鼠大脑的神经毒性与摄入剂量呈正相关，可能与γ-氨基丁酸的表达上调以及染毒后神经元的变性损伤有关。
 

关键词: 神经再生, 丙烯酰胺, 氨基丁酸, 胶质纤维酸性蛋白, 谷氨酸脱羧酶, 神经毒性, 断乳期, 脏器系数, 大脑, 皮质, 谷氨酸

Abstract:

The mechanism underlying acrylamide-induced neurotoxicity remains controversial. Previous studies have focused on acrylamide-induced toxicity in adult rodents, but neurotoxicity in weaning rats has not been investigated. To explore the neurotoxic effect of acrylamide on the developing brain, weaning rats were gavaged with 0, 5, 15, and 30 mg/kg acrylamide for 4 consecutive weeks. No obvious neurotoxicity was observed in weaning rats in the low-dose acrylamide group (5 mg/kg). However, rats from the moderate- and high-dose acrylamide groups (15 and 30 mg/kg) had an abnormal gait. Furthermore, biochemical tests in these rats demonstrated that glutamate concentration was significantly reduced, and γ-aminobutyric acid content was significantly increased and was dependent on acrylamide dose. Immunohistochemical staining showed that in the cerebral cortex, γ-aminobutyric acid, glutamic acid decarboxylase and glial fibrillary acidic protein expression increased remarkably in the moderate- and high-dose acrylamide groups. These results indicate that in weaning rats, acrylamide is positively associated with neurotoxicity in a dose-dependent manner, which may correlate with upregulation of γ-aminobutyric acid and subsequent neuronal degeneration after the initial acrylamide exposure.

Key words: nerve regeneration, γ-aminobutyric acid, glial fibrillary acidic protein, glutamic acid    , decarboxylase, neurotoxicity, weaning, organ index, cerebrum, cortex, glutamate, neural regeneration