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促红细胞生成素治疗脊髓损伤:对大鼠不同剂量及创伤程度的评估

Erythropoietin to Treat Spinal Cord Injury: Evaluation of Different Doses and Magnitudes of Trauma in Rats.

作者信息

Barros Alderico Girão Campos de, Dos Santos Gustavo Bispo, Marcon Raphael Martus, Cristante Alexandre Fogaça

机构信息

Department of Orthopedics and Traumatology, University of São Paulo Institute of Orthopedics and Traumatology, São Paulo, Brasil.

出版信息

Global Spine J. 2024 Dec 9:21925682241306106. doi: 10.1177/21925682241306106.

DOI:10.1177/21925682241306106
PMID:39652832
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11629366/
Abstract

STUDY DESIGN

Experimental spinal cord lesion study.

OBJECTIVES

To evaluate the effects of erythropoietin at different doses on neural regeneration in rats undergoing spinal cord injury.

METHODS

Anesthetized Wistar rats were submitted to standardized spinal cord injury and randomized into eight groups, receiving different magnitudes of trauma and single or repeated doses of intraperitoneal erythropoietin (500 or 5000 IU/kg of body weight). We evaluated motor function using BBB scores and sensorimotor behavior by observing the rats walking on a horizontal ladder (at 2, 4, and 6 weeks) and performed histological analysis of the spinal cord after euthanasia. We compared the scores between groups using analysis of variance (ANOVA) and Bonferroni multiple comparisons.

RESULTS

The experiments were conducted with 10 animals per group (n = 80), none of which died or were excluded. BBB scores increased over time (meaning recovery) in all groups ( < 0.001 for all). From the fourth week, animals receiving lower trauma and higher erythropoietin doses had higher BBB scores than those receiving lower doses. The total number of steps and correct steps taken on the horizontal ladder increased, and slips decreased over time with treatment in all groups. Although the number of errors was different between moments ( < 0.001), it was not different between groups ( = 0.707). Rats receiving higher impact lesions had more spinal cord necrosis and worse recovery of neuronal fibers than the rest.

CONCLUSIONS

Animals receiving a higher dose of erythropoietin and suffering minor trauma showed better and faster neurological recovery. Repeating erythropoietin after a week showed no benefit.

摘要

研究设计

实验性脊髓损伤研究。

目的

评估不同剂量促红细胞生成素对脊髓损伤大鼠神经再生的影响。

方法

将麻醉后的Wistar大鼠进行标准化脊髓损伤,并随机分为八组,接受不同程度的创伤以及单次或重复剂量的腹腔注射促红细胞生成素(500或5000国际单位/千克体重)。我们通过BBB评分评估运动功能,并通过观察大鼠在水平梯子上行走(在第2、4和6周)来评估感觉运动行为,在安乐死后对脊髓进行组织学分析。我们使用方差分析(ANOVA)和Bonferroni多重比较来比较组间得分。

结果

每组10只动物(n = 80)进行实验,无一死亡或被排除。所有组的BBB评分均随时间增加(意味着恢复)(所有P < 0.001)。从第四周开始,接受较低创伤和较高促红细胞生成素剂量的动物的BBB评分高于接受较低剂量的动物。随着治疗进行,所有组在水平梯子上行走的总步数和正确步数增加,滑倒次数减少。尽管不同时间点的错误数量不同(P < 0.001),但组间无差异(P = 0.707)。受到较高撞击损伤的大鼠比其他大鼠有更多的脊髓坏死和更差的神经纤维恢复。

结论

接受较高剂量促红细胞生成素且创伤较小的动物显示出更好、更快的神经恢复。一周后重复使用促红细胞生成素无益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/6accce4483f2/10.1177_21925682241306106-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/39698c4f8f7f/10.1177_21925682241306106-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/ba0addd5c037/10.1177_21925682241306106-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/0ef5c27e25c8/10.1177_21925682241306106-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/ac07e1f72ffb/10.1177_21925682241306106-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/a947d8d46720/10.1177_21925682241306106-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/6accce4483f2/10.1177_21925682241306106-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/39698c4f8f7f/10.1177_21925682241306106-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/ba0addd5c037/10.1177_21925682241306106-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/0ef5c27e25c8/10.1177_21925682241306106-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/ac07e1f72ffb/10.1177_21925682241306106-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/a947d8d46720/10.1177_21925682241306106-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e74e/12127679/6accce4483f2/10.1177_21925682241306106-fig6.jpg

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