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粒细胞集落刺激因子对脊髓损伤动物神经和运动功能的影响:一项系统评价和荟萃分析

Granulocyte colony-stimulating factor effects on neurological and motor function in animals with spinal cord injury: a systematic review and meta-analysis.

作者信息

Tao Jing-Wei, Fan Xiao, Zhou Jing-Ya, Huo Lu-Yao, Mo Yan-Jun, Bai Hui-Zhong, Zhao Yi, Ren Jing-Pei, Mu Xiao-Hong, Xu Lin

机构信息

Center for Orthopedic Surgery, Beijing University of Chinese Medicine Dongzhimen Hospital, Beijing, China.

Beijing University of Chinese Medicine, Beijing, China.

出版信息

Front Neurosci. 2023 Jun 28;17:1168764. doi: 10.3389/fnins.2023.1168764. eCollection 2023.

Abstract

BACKGROUND

Spinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat autologous bone marrow transplantation, chemotherapy-induced granulocytopenia, Acquired Immune Deficiency Syndrome (AIDS), etc. Recent research has revealed the potential application of G-CSF on neuroprotective effectiveness. In central nervous system diseases, G-CSF can be used to alleviate neuronal injury.

OBJECTIVE

To investigate the effects of G-CSF on Basso, Beattie, and Bresnahan (BBB) scale score, inclined plane test, electrophysiologic exam, quantitative analysis of TUNEL-positive cells, and quantitative analysis of glial fibrillary acidic protein (GFAP) immunostaining images in animal models of SCI.

METHODS

We searched PubMed, Web of Science, and Embase databases for all articles on G-CSF intervention with animal models of SCI reported before November 2022. A total of 20 studies met the inclusion criteria.

RESULTS

Results revealed that G-CSF intervention could improve the BBB scale score in both groups at 3, 7, 14, 28, and 35 days [at 35  days, weighted mean differences (WMD) = 2.4, 95% CI: 1.92-2.87,  < 0.00001, I = 69%]; inclined plane test score; electrophysiologic exam; quantitative analysis of TUNEL-positive cell numbers; quantitative analysis of GFAP immunostaining images in animal models of SCI. Subgroup analysis revealed that treatment with normal saline, phosphate-buffered saline, and no treatment resulted in significantly different neurological function effectiveness compared to the G-CSF therapy. SD rats and Wistar rats with SCI resulted in significant neurological function effectiveness. C57BL/6 mice showed no difference in the final effect. The T9-T10 or T10 segment injury model and the T8-T9 or T9 segment injury model resulted in significant neurological function effectiveness. The BBB score data showed no clear funnel plot asymmetry. We found no bias in the analysis result (Egger's test,  = 0.42). In our network meta-analysis, the SUCRA ranking showed that 15 mg/kg-20 mg/kg was an optimal dose for long-term efficacy.

CONCLUSION

Our meta-analysis suggests that G-CSF therapy may enhance the recovery of motor activity and have a specific neuroprotective effect in SCI animal models.: PROSPERO, identifier: CRD42023388315.

摘要

背景

脊髓损伤(SCI)是一种严重的神经损伤,目前尚无有效的治疗方法。粒细胞集落刺激因子(G-CSF)用于治疗自体骨髓移植、化疗引起的粒细胞减少症、获得性免疫缺陷综合征(AIDS)等。最近的研究揭示了G-CSF在神经保护方面的潜在应用。在中枢神经系统疾病中,G-CSF可用于减轻神经元损伤。

目的

探讨G-CSF对SCI动物模型的Basso、Beattie和Bresnahan(BBB)量表评分、斜板试验、电生理检查、TUNEL阳性细胞定量分析以及胶质纤维酸性蛋白(GFAP)免疫染色图像定量分析的影响。

方法

我们在PubMed、Web of Science和Embase数据库中搜索了2022年11月之前报道的所有关于G-CSF干预SCI动物模型的文章。共有20项研究符合纳入标准。

结果

结果显示,G-CSF干预可在第3、7、14、28和35天提高两组的BBB量表评分[在第35天,加权平均差(WMD)=2.4,95%CI:1.92-2.87,P<0.00001,I=69%];斜板试验评分;电生理检查;TUNEL阳性细胞数量的定量分析;SCI动物模型中GFAP免疫染色图像的定量分析。亚组分析显示,与G-CSF治疗相比,生理盐水、磷酸盐缓冲盐水治疗和未治疗导致神经功能有效性存在显著差异。SCI的SD大鼠和Wistar大鼠导致显著的神经功能有效性。C57BL/6小鼠在最终效果上没有差异。T9-T10或T10节段损伤模型以及T8-T9或T9节段损伤模型导致显著的神经功能有效性。BBB评分数据没有明显的漏斗图不对称性。我们在分析结果中未发现偏倚(Egger检验,P=0.42)。在我们的网络荟萃分析中,SUCRA排名显示15mg/kg-20mg/kg是长期疗效的最佳剂量。

结论

我们的荟萃分析表明,G-CSF治疗可能增强运动活动的恢复,并在SCI动物模型中具有特定的神经保护作用。:PROSPERO,标识符:CRD42023388315。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e2/10338098/2b60e1d91941/fnins-17-1168764-g001.jpg

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