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 (6): 1120-1132.doi: 10.4103/1673-5374.270419

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

调节自噬对脊髓损伤治疗效果的影响：直接和间接比较的网络meta分析

  

  • 出版日期:2020-06-15 发布日期:2020-07-05
  • 基金资助:
    中国北京市优秀人才培养基金（201700002469G215）；中国首都医科大学自然科学基金（PYZ2018081）；中国北京天坛医院青年科学基金（2016-YQN-14）

Therapeutic effect of regulating autophagy in spinal cord injury: a network meta-analysis of direct and indirect comparisons

Duo Zhang1, Di Zhu1, Fang Wang2, Ji-Chao Zhu1, Xu Zhai3, Yuan Yuan4, Chen-Xi Li1   

  1. 1 Department of Orthopedics, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
    2 Department of Orthopedics, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
    3 Department of Emergency, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
    4 Department of Spinal Cord Injury Rehabilitation, China Rehabilitation Research Center, Beijing, China
  • Online:2020-06-15 Published:2020-07-05
  • Contact: Duo Zhang, MD,zhangduo-88@163.com.
  • Supported by:
    This work was supported by the Beijing Excellent Talent Training Foundation of China, No. 2017000021469G215 (to DZhang); the Natural Science Foundation of Capital Medical University of China, No. PYZ2018081 (to DZhang); the Youth Science Foundation of Beijing Tiantan Hospital of China, No. 2016-YQN-14 (to DZhang).

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摘要：

目的：许多的研究表明，细胞自噬在脊髓损伤的发生、发展过程中起着重要作用，而调节自噬对脊髓损伤修复具有积极意义。如何调节自噬水平及对脊髓损伤治疗效果的影响仍有争议，在促进还是抑制自噬的问题上学术意见不一致。因此，文章应用直接和间接比较的方法，分析了自噬调节治疗大鼠脊髓损伤的效果，以期为将来更好的进行相关研究提供依据。

资料来源：以“脊髓损伤”、“自噬”、“大鼠”等关键词检索万方数据库、CNKI数据库中文数据库，Web of Science，Medline (OvidSP)，PubMed英文数据库及Google Scholar。语言限定为中文及英文，各数据库检索时间均为建库至2018年2月。

资料选择：纳入文献为调节自噬治疗脊髓损伤大鼠体内实验研究(包括脊髓损伤前及损伤后干预)。对纳入的各项研究在不同时间点进行meta分析直接比较促进自噬或抑制自噬的治疗效果，并进行亚组分析。

结局指标：结局指标为评估脊髓损伤大鼠神经功能的BBB评分。

结果：(1)检索到622篇文献中有33篇纳入研究，研究均具有较高质量。进行促进自噬干预后，脊髓损伤大鼠BBB评分在术后1 d (MD=1.80, 95% CI：0.81-2.79，P=0.0004)，3 d (MD=0.92, 95% CI：0.72-1.13，P < 0.00001)，1周(MD=2.39, 95% CI：1.85-2.92，P < 0.00001)，2周(MD=3.26, 95% CI：2.40-4.13，P < 0.00001)，3周(MD=3.13, 95% CI：2.51-3.75，P < 0.00001)，4周(MD=3.18, 95% CI：2.43-3.92，P < 0.00001)较空白对照组（药物溶剂对照，如生理盐水组）均升高；(2)而抑制自噬后，脊髓损伤大鼠BBB评分在术后1 d (MD=6.48, 95% CI： 5.83-7.13，P < 0.00001)，2周(MD=2.43, 95% CI： 0.79-4.07，P=0.004)，3周(MD=2.96, 95% CI： 0.09-5.84，P=0.04)，4周(MD=4.41, 95% CI： 1.08-7.75，P=0.010)较空白对照组更均升高；(3)间接比较结果提示，以空白对照组为中介，无论促进或抑制自噬，脊髓损伤大鼠BBB评分在术后1 d (MD= -4.68, 95% CI： -5.840 to -3.496，P=0.94644)，3 d (MD=-0.28, 95% CI：-2.231-1.671，P=0.99448)，1周(MD=1.83, 95% CI： 0.0076-3.584，P=0.94588)，2周(MD=0.81, 95% CI：-0.850-2.470，P=0.93055)，3周(MD=0.17, 95% CI：-2.771-3.111，P=0.99546)，4周(MD=-1.23, 95% CI： -4.647-2.187，P =0.98264)与空白对照组相比均无显著差异。

结论：调节自噬对大鼠脊髓损伤后神经功能恢复具有直接促进作用，促进自噬与抑制自噬均能够促进神经恢复。然而间接比较促进自噬和抑制自噬对治疗脊髓损伤效果无明显差异。提示由于目前研究方式的多样性、脊髓损伤后自噬特点的不确定及自噬监测方法的限制，导致不同学者的研究结果具有较大差异。因此，在以后的研究中，应当建立统一的标准化实验规范，并对自噬变化进行动态观察。

orcid: 0000-0001-9011-4316 (Duo Zhang)

关键词: 脊髓损伤, 自噬, 调节, 大鼠模型, 神经功能, BBB评分, 荟萃分析, 间接比较, 策略分析

Abstract:

Objective: An increasing number of studies indicate that autophagy plays an important role in the patho- genesis of spinal cord injury, and that regulating autophagy can enhance recovery from spinal cord injury. However, the effect of regulating autophagy and whether autophagy is detrimental or beneficial after spinal cord injury remain unclear. Therefore, in this study we evaluated the effects of autophagy regulation on spinal cord injury in rats by direct and indirect comparison, in an effort to provide a basis for further re- search.

Data source: Relevant literature published from inception to February 1, 2018 were included by searching Wanfang, CNKI, Web of Science, MEDLINE (OvidSP), PubMed and Google Scholar in English and Chi- nese. The keywords included “autophagy”, “spinal cord injury”, and “rat”.

Data selection: The literature included in vivo experimental studies on autophagy regulation in the treat- ment of spinal cord injury (including intervention pre- and post-spinal cord injury). Meta-analyses were conducted at different time points to compare the therapeutic effects of promoting or inhibiting autophagy, and subgroup analyses were also conducted.

Outcome measure: Basso, Beattie, and Bresnahan scores.

Results: Of the 622 studies, 33 studies of median quality were included in the analyses. Basso, Beattie, and Bresnahan scores were higher at 1 day (MD = 1.80, 95% CI: 0.81–2.79, P = 0.0004), 3 days (MD = 0.92, 95% CI: 0.72–1.13, P < 0.00001), 1 week (MD = 2.39, 95% CI: 1.85–2.92, P < 0.00001), 2 weeks (MD = 3.26, 95% CI: 2.40–4.13, P < 0.00001), 3 weeks (MD = 3.13, 95% CI: 2.51–3.75, P < 0.00001) and 4 weeks (MD = 3.18, 95% CI: 2.43–3.92, P < 0.00001) after spinal cord injury with upregulation of autophagy compared with the control group (drug solvent control, such as saline group). Basso, Beattie, and Bresnahan scores were higher at 1 day (MD = 6.48, 95% CI: 5.83–7.13, P < 0.00001), 2 weeks (MD = 2.43, 95% CI: 0.79–4.07, P = 0.004), 3 weeks (MD = 2.96, 95% CI: 0.09–5.84, P = 0.04) and 4 weeks (MD = 4.41, 95% CI: 1.08–7.75, P = 0.01) after spinal cord injury with downregulation of autophagy compared with the control group. Indirect comparison of upregulation and downregulation of autophagy showed no differences in Basso, Beattie, and Bresnahan scores at 1 day (MD = −4.68, 95% CI: –5.840 to −3.496, P = 0.94644), 3 days (MD = −0.28, 95% CI: −2.231–1.671, P = 0.99448), 1 week (MD = 1.83, 95% CI: 0.0076–3.584, P = 0.94588), 2 weeks (MD = 0.81, 95% CI: −0.850–2.470, P = 0.93055), 3 weeks (MD = 0.17, 95% CI: −2.771–3.111, P = 0.99546) or 4 weeks (MD = –1.23, 95% CI: −4.647–2.187, P = 0.98264) compared with the control group.

Conclusion: Regulation of autophagy improves neurological function, whether it is upregulated or down- regulated. There was no difference between upregulation and downregulation of autophagy in the treatment of spinal cord injury. The variability in results among the studies may be associated with differences in research methods, the lack of clearly defined autophagy characteristics after spinal cord injury, and the lim- ited autophagy monitoring techniques. Thus, methods should be standardized, and the dynamic regulation of autophagy should be examined in future studies.

Key words: autophagy, Basso, Beattie, and Bresnahan scores, indirect comparison, meta-analysis, nerve regeneration, neural regeneration, neurological function, rat models, regulation, spinal cord injury, strategy analysis