中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (8): 1279-1285.doi: 10.4103/1673-5374.162761

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

丹曲洛林可增强低温技术对损伤大脑皮质神经元的保护

  

  • 收稿日期:2015-07-21 出版日期:2015-08-24 发布日期:2015-08-24
  • 基金资助:

    广东省科技项目(2014A020212043),深圳市科技项目(JCYJ20140414170821242),深圳市合作创新计划项目(GJHZ20120614154914623),山西省委审计省委科技项目(201201060)

Dantrolene enhances the protective effect of hypothermia on cerebral cortex neurons

Sui-yi Xu1, 2, Feng-yun Hu3, Li-jie Ren2, Lei Chen2, Zhu-qing Zhou2, Xie-jun Zhang2, Wei-ping Li1, 2   

  1. 1 Postdoctoral Workstation, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China
    2 Department of Brain Center, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People’s Hospital, Shenzhen University First Affiliated Hospital, Shenzhen, Guangdong Province, China
    3 Department of Neurology, Shanxi Provincial People’s Hospital, Shanxi Medical University, Taiyuan, Shanxi Province, China
  • Received:2015-07-21 Online:2015-08-24 Published:2015-08-24
  • Contact: Wei-ping Li, M.D., Ph.D.,liweiping0755@sina.com.
  • Supported by:
    This work was supported by a grant from the Guangdong Science & Technology Plan Program in China, No. 2014A020212043; the a grant from the Shenzhen Science & Technology Plan Program in China, No. JCYJ20140414170821242; the a grant from Shenzhen Collaborative Innovation Plan Program in China, No. GJHZ20120614154914623; a grant from the Science & Technology Project of Shanxi Health and Family Planning Commission in China, No. 201201060.  

摘要:

低温治疗对缺血性损伤神经元有非药物的神经保护作用,但存在颤抖等不良反应。丹曲洛林对缺血损伤神经元也有神经保护作用,还能缓解低温治疗的不良反应,故实验假设丹曲洛林可能成为增强低温治疗缺血性卒中神经保护作用的辅助用药。分离E18胎鼠大脑皮质神经元,进行氧糖剥夺90min后复氧,33℃低温培养和/或40μM丹曲洛林干预12h。结果显示丹曲洛林联合低温干预后损伤神经元存活率增加,活性氧和游离钙浓度下降,线粒体膜电位增加,细胞质组蛋白相关的DNA片段化和细胞凋亡减少,细胞形态明显改善,效果优于单独丹曲洛林或单独低温干预。结果表明丹曲洛林可成为一种增强低温治疗缺血性卒中神经元保护的有效辅助治疗方法。

关键词: 神经再生, 神经元, 缺血性脑卒中, 氧糖剥夺, 荧光探针, 流式细胞术, 细胞凋亡, 钙超载, 活性氧

Abstract:

Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is neuroprotective in in vitro and in vivo ischemic injury models. In addition to its neuroprotective effect, dantrolene neutralizes the adverse reaction of hypothermia. Dantrolene may be an effective adjunctive therapy to enhance the neuroprotection of hypothermia in treating ischemic stroke. Cortical neurons isolated from rat fetuses were exposed to 90 minutes of oxygen-glucose deprivation followed by reoxygenation. Neurons were treated with 40 μM dantrolene, hypothermia (at 33°C), or the combination of both for 12 hours. Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis. Furthermore, improvements in cell morphology were observed. The combined treatment enhanced these responses compared with either treatment alone. These findings indicate that dantrolene may be used as an effective adjunctive therapy to enhance the neuroprotective effects of hypothermia in ischemic stroke.