中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (10): 1947-1954.doi: 10.4103/1673-5374.280326

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

阿托伐他汀对蛛网膜下腔出血的早期神经保护

  

  • 出版日期:2020-10-15 发布日期:2020-08-19
  • 基金资助:

    无锡科学技术发展基金(WX18IIAN041),南京军区重大基金项目(15DX003),无锡青年医学基金项目(QNRC046)

An early neuroprotective effect of atorvastatin against subarachnoid hemorrhage

Jun-Hui Chen1, 2, Ting Wu3, Wen-Yuan Xia4, Zhong-Hua Shi2, Chun-Lei Zhang2, Lei Chen2, Qian-Xue Chen1, Yu-Hai Wang2   

  1. 1 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
    2 Department of Neurosurgery, Wuxi Clinical College of Anhui Medical University, 904 Hospital of Joint Logistic Support Force of PLA, Wuxi, Jiangsu Province, China
    3 Department of Cardiology, Wuxi Clinical College of Anhui Medical University, 904 Hospital of Joint Logistic Support Force of PLA, Wuxi, Jiangsu Province, China
    4 Department of Science and Education, Wuxi Clinical College of Anhui Medical University, 904 Hospital of Joint Logistic Support Force of PLA, Wuxi, Jiangsu Province, China
  • Online:2020-10-15 Published:2020-08-19
  • Contact: Yu-Hai Wang,wangyuhai67@126.com; Qian-Xue Chen,chenqx666@whu.edu.cn.
  • Supported by:
    This study was supported by the Wuxi Foundation for Development of Science and Technology of China, No. WX18IIAN041 (to JHC); the Major Project of Nanjing Military Area Research Fund of China, No. 15DX003 (to JHC); the Wuxi Youth Medical Fund of China, No. QNRC046 (to TW).

摘要:

阿托伐他汀可减少蛛网膜下腔出血后早期脑水肿和神经元死亡,但其作用机制尚不清楚。实验以小脑延髓池注射自体血建立蛛网膜下腔出血大鼠模型,在损伤前24h以及损伤后12和36h灌胃20 mg/kg阿托伐他汀进行治疗。结果发现,蛛网膜下腔出血损伤后72h时,蛛网膜下腔出血大鼠的神经功能明显改善,脑水肿明显减轻,大脑皮质中神经元凋亡明显减少,自噬相关蛋白Beclin-1阳性细胞数量增加,Beclin-1和LC3的蛋白表达增加,颞叶组织中神经元超微结构损伤显著减轻,其表现与损伤后脑室内注射激活自噬信号通路的雷帕霉素结果相似,而与注射抑制自噬信号通路的3-甲基腺嘌呤的结果相反。提示阿托伐他汀可通过激活自噬对蛛网膜下腔出血发挥早期神经保护作用。实验于2017年2月22日经安徽医科大学伦理委员会(解放军联合后勤支援部队904医院)批准,批准号YXLL-2017-09。

orcid: 0000-0001-6983-8547 (Qian-Xue Chen)

关键词:

蛛网膜下腔出血, 阿托伐他汀, 自噬, 早期脑损伤, 3-甲基腺嘌呤, LC3, 雷帕霉素, 细胞凋亡, 神经保护

Abstract: Atorvastatin has been shown to reduce early brain edema and neuronal death after subarachnoid hemorrhage, but its mechanism is not clear. In this study, rat models of subarachnoid hemorrhage were established by autologous blood injection in the cisterna magna. Rat models were intragastrically administered 20 mg/kg atorvastatin 24 hours before subarachnoid hemorrhage, 12 and 36 hours after subarachnoid hemorrhage. Compared with the controls, atorvastatin treatment demonstrated that at 72 hours after subarachnoid hemorrhage, neurological function had clearly improved; brain edema was remarkably relieved; cell apoptosis was markedly reduced in the cerebral cortex of rats; the number of autophagy-related protein Beclin-1-positive cells and the expression levels of Beclin-1 and LC3 were increased compared with subarachnoid hemorrhage only. The ultrastructural damage of neurons in the temporal lobe was also noticeably alleviated. The similarities between the effects of atorvastatin and rapamycin were seen in all the measured outcomes of subarachnoid hemorrhage. However, these were contrary to the results of 3-methyladenine injection, which inhibits the signaling pathway of autophagy. These findings indicate that atorvastatin plays an early neuroprotective role in subarachnoid hemorrhage by activating autophagy. The experimental protocol was approved by the Animal Ethics Committee of Anhui Medical University, China (904 Hospital of Joint Logistic Support Force of PLA; approval No. YXLL-2017-09) on February 22, 2017.

Key words: 3-methyladenine, apoptosis, atorvastatin, autophagy, early brain injury, LC3, neuroprotection, rapamycin, subarachnoid hemorrhage