中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (11): 1919-1931.doi: 10.4103/1673-5374.259619

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

MK-801减缓大鼠急性脑损伤后病灶体积扩散的meta分析

  

  • 出版日期:2019-11-15 发布日期:2019-11-15
  • 基金资助:
    国家自然科学基金（81822050，81873321，81673990，81330085，81730107）; 上海市卫生和计划生育委员会中国中医研究项目（2018JP014）; 中国市级医院临床技能和临床创新三年行动计划（16CR1017A）; 上海市中医慢性病[恶性肿瘤，骨退行性疾病]中国临床医学中心项目项目（2017ZZ01010）; 中国教育部创新团队项目（IRT1270）; 中国科学技术部重点领域创新团队想项目（2015RA4002）; 中国上海市长宁区光华医院杰出原则研究项目（2016 - 01，2016-06）

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis

Nan-Xing Yi 1, 2, 3 , Long-Yun Zhou 2, 3, 4 , Xiao-Yun Wang 1 , Yong-Jia Song 1, 2, 3 , Hai-Hui Han 2, 5 , Tian-Song Zhang 6 , Yong-Jun Wang 2, 3 , Qi Shi 1, 2, 3, 5 , Hao Xu 1, 2, 3 , Qian-Qian Liang 1, 2, 3 , Ting Zhang 1, 2   

  1. 1 Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
    2 Institute of Spine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    3 Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, China
    4 School of Rehabilitation Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    5 Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
    6 Jing’an District Center Hospital, Fudan University, Shanghai, China
  • Online:2019-11-15 Published:2019-11-15
  • Contact: Hao Xu, PhD, HOXU@163.com; Qian-Qian Liang, PhD, liangqianqiantcm@126.com; Ting Zhang, PhD, ztingdd@hotmail.com.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81822050, 81873321, 81673990, 81330085 , 81730107; the Shanghai Municipal Health and Family Planning Commission TCM Research Project of China, No. 2018JP014 ; the Three-Year Action Plan to Promote Clinical Skills and Clinical Innovation in Municipal Hospitals of China, No. 16CR1017A; the Shanghai Traditional Chinese Medicine Chronic Disease [Malignant Tumor, Bone Degenerative Disease] Clinical Medical Center of China, No. 2017ZZ01010; the National Ministry of Education Innovation Team of China, No. IRT1270; the Innovation Team of Key Fields of the Ministry of Science and Technology of China, No. 2015RA4002.  

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摘要：

目的：评价MK-801在急性脑损伤大鼠模型中的应用效果，观察其对大鼠急性脑损伤后病灶体积的影响。
数据来源：使用关键检索词“卒中”“脑疾病”“脑损伤”“脑出血、创伤性脑损伤”“急性脑损伤”“马来酸盐地佐昔平”“地佐昔平”“MK-801”“MK801”和“大鼠”等。检索PubMed、Cochrane library、EMBASE、中国知网(CNKI)数据库、万方数据库、维普(VJIP)和SinoMed数据库，检索时间截止2018年3月。
数据选择：选择报道MK-801治疗实验性急性脑损伤大鼠的研究。两位研究人员独立进行文献筛选、数据提取和方法学质量评估。
结局指标：主要指标包括病变体积和脑水肿；次要指标包括脑损伤后24 h的贝德森神经系统神经功能评估和水迷宫试验结果。
结果：文章共纳入52项符合条件的研究，共2530个样本，其中17项具有较高的方法学质量。总体上，MK-801实验组大鼠脑病灶体积(34篇，n=966，MD=-58.31，95% CI: -66.55 to -50.07，P < 0.00001)和脑水肿程度(5篇，n=75，MD=-1.21, 95% CI: -1.50 to -0.91，P < 0.00001)明显低于对照组。MK-801能改善水迷宫中大鼠的空间认知能力(2篇，n=60，MD=-10.88, 95% CI: -20.75 to -1.00，P=0.03)以及脑损伤后24 h的神经功能评分(11篇，n=335，MD=-1.04，95% CI: -1.47 to -0.60，P < 0.00001)。亚组分析提示病灶体积在不同损伤模型下减小的程度不同(34篇，n=966，MD=-58.31，95% CI：-66.55 to -50.07，P=0.004)。进一步的网络分析表明，0-1 mg/kg MK-801可能是治疗MCAO模型的最佳剂量。
结论：MK-801能有效减小实验性急性脑损伤大鼠大脑病灶体积，减轻脑水肿程度，对急性脑损伤有较好的神经保护效应。同时，其兼备良好的安全性及初步揭示的疗效机制，有着进一步向临床转化的前景。

orcid: 0000-0002-8311-506X(Hao Xu)
          0000-0001-8797-7778(Qian-Qian Liang)
          0000-0001-9399-4734(Ting Zhang)

关键词: 急性脑损伤, 神经功能, 空间认知, 水迷宫试验, 病灶体积, 脑水肿, 大鼠, 系统评价, Meta分析

Abstract:

OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.
DATA SOURCES: Key terms were “stroke”, “brain diseases”, “brain injuries”, “brain hemorrhage, traumatic”, “acute brain injury”, “dizocilpine maleate”, “dizocilpine”, “MK-801”, “MK801”, “rat”, “rats”, “rattus” and “murine”. PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform (VJIP) and SinoMed databases were searched from their inception dates to March 2018.
DATA SELECTION: Studies were selected if they reported the effects of MK-801 in  xperimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.
OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury.
RESULTS:  A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume (34 studies, n = 966, MD = −58.31, 95% CI: −66.55 to −50.07; P < 0.00001) and degree of cerebral edema (5 studies, n = 75, MD = −1.21, 95% CI: −1.50 to −0.91; P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test (2 studies, n = 60, MD = −10.88, 95% CI: −20.75 to −1.00; P = 0.03) and neurological function 24 hours after brain injury (11 studies, n = 335, MD = −1.04, 95% CI: −1.47 to −0.60; P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models (34 studies, n = 966, MD = −58.31, 95% CI: −66.55 to −50.07; P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model.
CONCLUSION: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.

Key words: nerve regeneration, acute brain injury, neurological function, spatial cognition, water maze test, lesion volume, brain edema, rat, systematic review, meta-analysis, neural regeneration