中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (3): 537-547.doi: 10.4103/1673-5374.266065

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

二十二碳六烯酸对脊髓损伤大鼠运动功能恢复的影响：一项Meta分析

  

  • 出版日期:2020-03-15 发布日期:2020-05-26
  • 基金资助:
    国家自然科学基金（81704096，81603635， 81873317）的支持; 上海市科学技术委员会-中医药重点项目（16401970100）; 中国慢性病上海中医药中心项目（2017ZZ01010）; 国家新药开发与开发第十五个五年科技重大专项基金（2017ZX09304001）; 中国科学技术部创新研究组计划（2015RA4002）; 中国“创新团队”发展项目（IRT1270）; 加快中国传统医药计划发展的三年行动项目[2018-2020）-CCCX-3003]

Effect of docosahexaenoic acid on the recovery of motor function in rats with spinal cord injury: a meta-analysis

Zi-Rui Tian1, 2, 3, Min Yao1, 2, Long-Yun Zhou2, 3, 4, Yong-Jia Song1, 2, 3, Jie Ye5, Yong-Jun Wang1, 2, 3, 4, Xue-Jun Cui1, 2   

  1. 1 Institute of Spine Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    2 Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of Traditional Chinese Medicine), Shanghai, China
    3 Shanghai University of Traditional Chinese Medicine, Shanghai, China
    4 Rehabilitation Medicine College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    5 Department of Orthopedics and Traumatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • Online:2020-03-15 Published:2020-05-26
  • Contact: Xue-Jun Cui, PhD,13917715524@139.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81704096, 81603635, 81873317 (to MY, JY, XJC); Shanghai Science and Technology Commission - Key Project of Traditional Chinese Medicine, No. 16401970100 (to YJW); the Shanghai Traditional Chinese Medicine Medical Center of Chronic Disease of China, No. 2017ZZ01010 (to YJW); the National Thirteenth Five-Year Science and Technology Major Special Project for New Drug Innovation and Development of China, No. 2017ZX09304001 (to YJW); the Program for Innovative Research Team of Ministry of Science and Technology of China, No. 2015RA4002 (to YJW); the “Innovation Team” Development Projects of China, No. IRT1270 (to YJW); the Three Years Action to Accelerate the Development of Traditional Chinese Medicine Plan of China, No. ZY(2018-2020)-CCCX-3003 (to YJW).

PDF

147

摘要：

目的：研究表明二十二碳六烯酸(DHA)在脊髓损伤的治疗中有一定价值。通过meta分析的方法，讨论DHA对大鼠脊髓损伤模型神经恢复的作用，以及脊髓损伤后运动功能恢复与给药时间、给药剂型和给药剂量的关系。

资料来源：在PubMed、Ebsco Medline、EMBASE、中国知网、万方、维普和中国生物医学文献数据库检索关于DHA治疗大鼠脊髓损伤的动物实验，检索时间设定为建库至2019年1月，检索词包括“脊髓损伤”、“脊髓疾病”、“脊髓创伤”、“二十二碳六烯酸”、“DHA”、“多聚不饱和脂肪酸”、“多不饱和脂肪酸”、“长链多价不饱和脂肪酸”、“脂肪酸”、“鼠”和“大鼠”等。

资料选择：选择纳入DHA治疗大鼠脊髓损伤后运动功能恢复的动物实验研究。其中实验组给予任何形式的DHA干预，对照组采用生理盐水、媒介溶液干预或无治疗措施。对纳入文献质量评估采用SYRCLE’s RoB tool评估工具。文献纳入、质量评价和资料提取由2名研究人员进行，对符合纳入标准的研究进行Meta分析。采用RevMan 5.1.2对数据进行统计分析。

结局评价指标：BBB评分作为主要结局指标，斜板试验、平衡木试验、楼梯试验、网格探索试验作为次要结局指标。

结果：总共纳入12篇相关文献，其中3篇文献质量较高，其余9篇文献质量较低。脊髓损伤大鼠接受DHA治疗后，BBB评分在治疗后第42天达到最高，在治疗后第21天，DHA组与对照组之间BBB评分差异最显著[pooled MD = 4.14; 95% CI = 3.58-4.70; P < 0.00001]。亚组分析中DHA静脉注射[pooled MD = 2.74; 95% CI = 1.41-4.07; P < 0.0001]和皮下注射[pooled MD = 2.99; 95% CI = 2.29-3.69; P < 0.00001]较口服[pooled MD = 3.04; 95% CI = -1.01 to 7.09; P = 0.14]对BBB评分改善效果更显著。DHA静脉注射250 nmol/kg[pooled MD = 2.94; 95% CI = 2.47-3.41; P < 0.00001]和1000 nmol/kg[pooled MD = 3.60; 95% CI = 2.66-4.54; P < 0.00001]均可明显提高大鼠BBB评分，促进运动功能恢复。

结论：分析结果显示，DHA在大鼠脊髓损伤后的功能恢复方面有促进作用，通过静脉注射和皮下注射DHA的给药方式较口服DHA有更好的疗效，DHA静脉注射250 nmol/kg与1000 nmol/kg均有良好的效果。因入组分析文章数量较少和文献质量较低，故确认结果，需要更多的高质量研究数据。

orcid: 0000-0002-9006-4547 (Xue-Jun Cui)

关键词: DHA, 二十二碳六烯酸, 多不饱和脂肪酸, 不饱和脂肪酸, 脂肪酸, 运动功能, 运动功能恢复, 脊髓损伤, 荟萃分析, 系统评价, 神经再生

Abstract:

Objective: Studies have shown that docosahexaenoic acid (DHA) has a beneficial effect in the treatment of spinal cord injury. A meta-analysis was used to study the effect of DHA on the neurological recovery in the rat spinal cord injury model, and the relationship between the recovery of motor function after spinal cord injury and the time and method of administration and the dose of DHA.

Data source: Published studies on the effect of DHA on spinal cord injury animal models from seven databases were searched from their inception to January 2019, including PubMed, MEDLINE, EMBASE, the China National Knowledge Infrastructure, Wanfang, VIP, and SinoMed databases. The search terms included “spinal cord injury” “docosahexaenoic acid”, and “rats”.

Data selection: Studies that evaluated the influence of DHA in rat models of spinal cord injury for locomotor functional recovery were included. The intervention group included any form of DHA treatment and the control group included treatment with normal saline, vehicle solution or no treatment. The Systematic Review Centre for Laboratory animal Experimentation’s risk of bias assessment tool was used for the quality assessment of the included studies. Literature inclusion, quality evaluation and data extraction were performed by two researchers. Meta-analysis was then conducted on all studies that met the inclusion criteria. Statistical analysis was performed on the data using RevMan 5.1.2. software.

Outcome measures: The primary outcome measure was the score on the Basso, Beattie, and Bresnahan scale. Secondary outcome measures were the sloping plate test, balance beam test, stair test and grid exploration test.

Results: A total of 12 related studies were included, 3 of which were of higher quality and the remaining 9 were of lower quality. The highest mean Basso, Beattie, and Bresnahan scale score occurred at 42 days after DHA treatment in spinal cord injury rats. At 21 days after treatment, the mean difference in Basso, Beattie, Bresnahan scores between the DHA group and the control group was the most significant (pooled MD = 4.14; 95% CI = 3.58–4.70; P < 0.00001). In the subgroup analysis, improvement in the Basso, Beattie, and Bresnahan scale score was more significant in rats administered DHA intravenously (pooled MD = 2.74; 95% CI = 1.41–4.07; P < 0.0001) and subcutaneously (pooled MD = 2.99; 95% CI = 2.29–3.69; P < 0.00001) than in the groups administered DHA orally (pooled MD = 3.04; 95% CI = –1.01 to 7.09; P = 0.14). Intravenous injection of DHA at 250 nmol/kg (pooled MD = 2.94; 95% CI = 2.47–3.41; P < 0.00001] and 1000 nmol/kg [pooled MD = 3.60; 95% CI = 2.66–4.54; P < 0.00001) significantly improved the Basso, Beattie, and Bresnahan scale score in rats and promoted the recovery of motor function.

Conclusion: DHA can promote motor functional recovery after spinal cord injury in rats. The administration of DHA by intravenous or subcutaneous injection is more effective than oral administration of DHA. Intravenous injection of DHA at doses of 250 nmol/kg or 1000 nmol/kg is beneficial. Because of the small number and the low quality of the included studies, more high-quality research is needed in future to substantiate the results.

Key words: DHA, docosahexaenoic acid, fatty acid, meta-analysis, motor function, motor function recover, polyunsaturated fatty acid, PUFA, spinal cord injury, systematic review