中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (6): 977-982.doi: http://orcid.org/0000-0002-6308-2870

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

阿托伐他汀激活脊髓损伤后细胞自噬及促进神经功能的恢复

  

  • 收稿日期:2015-12-22 出版日期:2016-06-30 发布日期:2016-06-30
  • 基金资助:

    国家自然科学基金（81471854）

Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury

Shuang Gao1, #, Zhong-ming Zhang2, #, Zhao-liang Shen2, Kai Gao3, Liang Chang4, Yue Guo5, Zhuo Li2, Wei Wang6, Ai-mei Wang1, *   

  1. 1 Department of Physiology, Jinzhou Medical University, Jinzhou, Liaoning Province, China 2 Department of Orthopedics, Jinzhou Municipal Second Hospital, Jinzhou, Liaoning Province, China 3 Department of Orthopedics, Jining No. 1 People’s Hospital, Jining, Shandong Province, China 4 Jinzhou Central Hospital, Jinzhou, Liaoning Province, China 5 Department of Orthopedics, Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, China 6 Department of Orthopedics, First Hospital of Qinhuangdao City, Qinhuangdao, Hebei Province, China
  • Received:2015-12-22 Online:2016-06-30 Published:2016-06-30
  • Contact: Ai-mei Wang, M.D., 505666670@qq.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81471854.

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摘要：

近来研究发现，作为降脂药物的阿托伐他汀具有神经保护作用，但具体机制不明。课题组以往研究结果也发现，脊髓损伤后细胞的自噬活动被激活，有利于神经功能的恢复。实验假设阿托伐他汀可激活脊髓损伤后细胞的自噬，从而促进神经功能恢复。实验应用改良Allen, s法建立脊髓损伤大鼠模型，并且在脊髓损伤后立即和第1，2天腹腔注射5 mg/kg阿托伐他汀。脊髓损伤后第7天，Western blot，RT-PCR，TUNEL染色结果显示，阿托伐他干预组大鼠脊髓组织中自噬标记性蛋白Beclin-1和LC3-B基因及蛋白表达均上调，细胞凋亡相关蛋白caspase-9和caspase-3表达下调，TUNEL染色阳性细胞数量减少；与单纯脊髓损伤模型大鼠相比，脊髓损伤后第14-42 d，阿托伐他干预组大鼠后肢BBB评分明显升高；说明阿托伐他汀可激活脊髓损伤后细胞的自噬，抑制细胞凋亡，促进损伤脊髓神经功能和恢复。 

orcid: 0000-0002-6308-2870 (Ai-mei Wang)

关键词: 神经再生, 脊髓损伤, 继发性损伤, 他汀类药物, 阿托伐他汀, 自噬, Beclin-1, LC3-B, 细胞凋亡, 神经保护性作用, 运动功能恢复, 国家自然科学基金

Abstract:

Atorvastatin, a lipid-lowering medication, provides neuroprotective effects, although the precise mechanisms of action remain unclear. Our previous studies confirmed activated autophagy following spinal cord injury, which was conducive to recovery of neurological functions. We hypothesized that atorvastatin could also activate autophagy after spinal cord injury, and subsequently improve recovery of neurological functions. A rat model of spinal cord injury was established based on the Allen method. Atorvastatin (5 mg/kg) was intraperitoneally injected at 1 and 2 days after spinal cord injury. At 7 days post-injury, western blot assay, reverse transcription-polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining results showed increased Beclin-1 and light chain 3B gene and protein expressions in the spinal cord injury + atorvastatin group. Additionally, caspase-9 and caspase-3 expression was decreased, and the number of TUNEL-positive cells was reduced. Compared with the spinal cord injury + saline group, Basso, Beattie, and Bresnahan locomotor rating scale scores significantly increased in the spinal cord injury + atorvastatin group at 14–42 days post-injury. These findings suggest that atorvastatin activated autophagy after spinal cord injury, inhibited apoptosis, and promoted recovery of neurological function.

Key words: nerve regeneration, spinal cord injury, secondary injury, statins, atorvastatin, autophagy, Beclin-1, light chain 3B, neuroprotection, apoptosis, motor function recovery, neural regeneration