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高压氧和促红细胞生成素联合治疗抑制脊髓损伤大鼠神经元凋亡并促进其恢复。

Combination Therapy With Hyperbaric Oxygen and Erythropoietin Inhibits Neuronal Apoptosis and Improves Recovery in Rats With Spinal Cord Injury.

机构信息

Department of Orthopedics, Shaoxing People's Hospital, Shaoxing, China; Department of Orthopedics and The Experimental Center, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Department of Orthopedics, The Second Affiliated Hospital of Soochow University.

出版信息

Phys Ther. 2019 Dec 16;99(12):1679-1689. doi: 10.1093/ptj/pzz125.

DOI:10.1093/ptj/pzz125

PMID:31504911

Abstract

BACKGROUND

Apoptosis plays an important role in various diseases, including spinal cord injury (SCI). Hyperbaric oxygen (HBO) and erythropoietin (EPO) promote the recovery from SCI, but the relationship between apoptosis and the combination therapeutic effect is not completely clear.

OBJECTIVE

The purpose of this study was to investigate the effects of HBO and EPO on SCI and the mechanisms that underlie their therapeutic benefits.

DESIGN

The study was designed to explore the effects of HBO and EPO on SCI through a randomized controlled trial.

METHODS

Sixty young developing female Sprague-Dawley rats were randomly divided into groups of 12 rats receiving sham, SCI, HBO, EPO, or HBO plus EPO. The SCI model was modified with the Allen method to better control consistency. HBO was performed for 1 hour per day for a total of 21 days, and EPO was given once per week for a total of 3 weeks. Both methods were performed 2 hours after SCI. Locomotor function was evaluated with the 21-point Basso-Beattie-Bresnahan Locomotor Rating Scale, an inclined-plane test, and a footprint analysis. All genes were detected by Western blotting and immunohistochemistry. The level of cell apoptosis was determined by Hoechst staining.

RESULTS

The results showed that HBO and EPO promoted the recovery of locomotor function in the hind limbs of rats by inhibiting the apoptosis of neurons. During this period, the expression of B-cell lymphoma/leukemia 2 protein (Bcl-2) increased significantly, whereas the expression of Bcl-2-associated X protein (Bax) and cleaved caspase 3 decreased significantly, indicating the inhibition of apoptosis. Meanwhile, the expression of G protein-coupled receptor 17 decreased, and that of myelin basic protein increased, suggesting that there may be a potential connection between demyelination and neuronal apoptosis.

LIMITATIONS

The limitations of the study include deviations in the preparation of SCI models; lack of reverse validation of molecular mechanisms; absence of in vitro cell experiments; and only one time point after SCI was studied.

CONCLUSIONS

HBO and EPO treatments are beneficial for SCI, especially when the 2 therapies are combined.

摘要

背景

细胞凋亡在包括脊髓损伤（SCI）在内的各种疾病中发挥着重要作用。高压氧（HBO）和促红细胞生成素（EPO）可促进 SCI 的恢复，但凋亡与联合治疗效果之间的关系尚不完全清楚。

目的

本研究旨在探讨 HBO 和 EPO 对 SCI 的影响及其治疗益处的机制。

设计

本研究通过随机对照试验设计来探讨 HBO 和 EPO 对 SCI 的影响。

方法

将 60 只年轻发育雌性 Sprague-Dawley 大鼠随机分为假手术、SCI、HBO、EPO 和 HBO+EPO 组，每组 12 只。采用 Allen 法改良 SCI 模型，以更好地控制一致性。HBO 每天 1 次，每次 1 小时，共 21 天；EPO 每周 1 次，共 3 周。两种方法均在 SCI 后 2 小时进行。采用 21 点 Basso-Beattie-Bresnahan 运动评分、斜板试验和足迹分析评估运动功能。通过 Western blot 和免疫组织化学检测所有基因。通过 Hoechst 染色检测细胞凋亡水平。

结果

结果显示，HBO 和 EPO 通过抑制神经元凋亡促进大鼠后肢运动功能的恢复。在此期间，B 细胞淋巴瘤/白血病 2 蛋白（Bcl-2）的表达显著增加，而 Bcl-2 相关 X 蛋白（Bax）和 cleaved caspase 3 的表达显著降低，表明凋亡受到抑制。同时，G 蛋白偶联受体 17 的表达降低，髓鞘碱性蛋白的表达增加，提示脱髓鞘与神经元凋亡之间可能存在潜在联系。