中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (2): 312-318.doi: 10.4103/1673-5374.290899

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

脑酐肌肽对缺血性脑卒中溶栓时间窗外的神经保护

  

  • 出版日期:2021-02-15 发布日期:2020-12-03
  • 基金资助:

    这项研究得到了中国博士后科学基金63期一级经费项目（2018M631061），澳门青年学者计划项目（AM201918）

Neuroprotection by cattle encephalon glycoside and ignotin beyond the time window of thrombolysis in ischemic stroke

Jun Zhong1, #, Rong-Wei Li1, 2, #, Ju Wang1, Ying Wang3, Hong-Fei Ge1, Ji-Shu Xian1, Hua Feng1, Liang Tan1, 4, *#br#   

  1. 1 Department of Neurosurgery, Southwest Hospital, The Third Military Medical University (Army Medical University), Chongqing, China;  2 Department of Neurosurgery, Hanzhong Central Hospital, Hanzhong, Shaanxi Province, China;  3 Department of Oncology, Hanzhong Central Hospital, Hanzhong, Shaanxi Province, China;  4 State Key Laboratory of Power Transmission Equipment and System Security and New Technology, School of Electrical Engineering, Chongqing University, Chongqing, China
  • Online:2021-02-15 Published:2020-12-03
  • Contact: Liang Tan, MD, PhD, tracy200712@hotmail.com. #Both authors contributed equally to this study.
  • Supported by:
    This study was supported by the 63rd Batch of First-Class Financing for Chinese Postdoctoral Science Foundation, No. 2018M631061 (to LT) and Macao Youth Scholars Program, No. AM201918 (to LT).

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摘要：

脑酐肌肽是一种由多肽、单唾液酸四己糖神经节苷脂、游离氨基酸等组成的多靶点神经保护药物，已被中国食药监局批准用于治疗卒中、阿尔茨海默病等疾病，但对超过4.5h溶栓时间窗的脑卒中患者的神经保护作用尚不清楚。实验首先以线栓法构建大鼠大脑中动脉闭塞模型模拟缺血性脑卒中，然后在缺血后8h起腹腔注射脑酐肌肽4 mL/kg，1次/d，连续治疗14d。然后以用改良的5点Bederson量表、平衡木试验以及转棒实验结果显示：（1）经4 mL/kg脑酐肌肽治疗的大鼠，其神经功能得到明显改善，但14d内的死亡率没有明显改善；（2）经脑MRI和TTC染色证实，接受治疗大鼠脑梗死体积明显缩小，电镜及双标免疫荧光染色结果可见缺血半暗带中海马神经元坏死减少，同时新生神经元特异性蛋白DCX阳性反应增强，其与增殖标志物Ki67双标阳性细胞数量增加；（3）上述结果说明，脑酐肌肽在超过溶栓时间后使用，依然对脑卒中病理改变发挥有效的神经保护作用。实验经陆军军医大学动物伦理委员会批准。

https://orcid.org/0000-0002-6916-2134 (Liang Tan)

关键词: 中枢神经系统, 脑, 卒中, 再生, 可塑性, 神经功能, 凋亡, 鼠

Abstract: Cattle encephalon glycoside and ignotin (CEGI) injection is known as a multi-target neuroprotective drug that contains numerous liposoluble molecules, such as polypeptides, monosialotetrahexosyl ganglioside (GM-1), free amino acids, hypoxanthine and carnosine. CEGI has been approved by the Chinese State Food and Drug Administration and widely used in the treatments of various diseases, such as stroke and Alzheimer’s disease. However, the neuroprotective effects of CEGI beyond the time window of thrombolysis (within 4.5 hours) on acute ischemic stroke remain unclear. This study constructed a rat middle cerebral artery occlusion model by suture-occluded method to simulate ischemic stroke. The first daily dose was intraperitoneally injected at 8 hours post-surgery and the CEGI treatments continued for 14 days. Results of the modified five-point Bederson scale, beam balance test and rotameric test showed the neurological function of ischemic stroke rats treated with 4 mL/kg/d CEGI improved significantly, but the mortality within 14 days did not change significantly. Brain MRI and 2,3,5-triphenyltetrazolium chloride staining confirmed that the infarct size in the 4 mL/kg/d CEGI-treated rats was significantly reduced compared with ischemic insult only. The results of transmission electron microscopy and double immunofluorescence staining showed that the hippocampal neuronal necrosis in the ischemic penumbra decreased whereas the immunopositivity of new neuronal-specific protein doublecortin and the percentage of Ki67/doublecortin positive cells increased in CEGI-treated rats compared with untreated rats. Our results suggest that CEGI has an effective neuroprotective effect on ischemic stroke when administered after the time window of thrombolysis. The study was approved by the Animal Ethics Committee of The Third Military Medical University, China.

Key words: apoptosis, brain, cattle encephalon glycoside and ignotin, central nervous system, neurological function, plasticity, rat, regeneration, stroke