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基于间充质干细胞的治疗可改善大鼠脊髓缺血后下肢运动功能。

Mesenchymal Stem Cell-Based Therapy Improves Lower Limb Movement After Spinal Cord Ischemia in Rats.

机构信息

Department of Cardiovascular Surgery, Hiroshima University Hospital, Hiroshima, Japan.

Department of Bio-Environmental Adaptation Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.

出版信息

Ann Thorac Surg. 2018 May;105(5):1523-1530. doi: 10.1016/j.athoracsur.2017.12.014. Epub 2018 Jan 12.

DOI:10.1016/j.athoracsur.2017.12.014
PMID:29337123
Abstract

BACKGROUND

Spinal cord ischemia is a devastating complication after thoracic and thoracoabdominal aortic operations. In this study, we aimed to investigate the effects of mesenchymal stem cells (MSCs), which have regenerative capability and exert paracrine actions on damaged tissues, injected into rat models of spinal cord ischemia-reperfusion injury.

METHODS

Forty-five Sprague-Dawley rats were divided into sham, phosphate-buffered saline (PBS), and MSC groups. Spinal cord ischemia was induced in the latter two groups by balloon occlusion of the thoracic aorta. MSCs and PBS were then immediately injected into the left carotid artery of the MSC and PBS groups, respectively. Hindlimb motor function was evaluated at 6 and 24 hours. The spinal cord was removed at 24 hours after ischemia-reperfusion injury, and histologic and immunohistochemical analyses and real-time polymerase chain reaction assessments were performed.

RESULTS

Rats in the MSC and PBS groups showed flaccid paraparesis/paraplegia postoperatively. Hindlimb function was significantly better at 6 and 24 hours after ischemia-reperfusion injury in the MSC group than in the PBS group (p < 0.05). The number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive neuron cells in the spinal cord and the ratio of Bax to Bcl2 were significantly larger (p < 0.05) in the PBS group than in the MSC group. The injected MSCs were observed in the spinal cord 24 hours after ischemia-reperfusion injury.

CONCLUSIONS

The MSC therapy by transarterial injection immediately after spinal cord ischemia-reperfusion injury may improve lower limb function by preventing apoptosis of neuron cells in the spinal cord.

摘要

背景

脊髓缺血是胸主动脉和胸腹主动脉手术后一种破坏性的并发症。在这项研究中,我们旨在研究间充质干细胞(MSCs)对脊髓缺血再灌注损伤大鼠模型的作用。MSCs 具有再生能力,并对受损组织发挥旁分泌作用。

方法

45 只 Sprague-Dawley 大鼠分为假手术组、磷酸盐缓冲液(PBS)组和 MSC 组。后两组通过气囊阻塞胸主动脉诱导脊髓缺血。然后,MSCs 和 PBS 分别立即注入 MSC 和 PBS 组的左侧颈总动脉。在缺血再灌注损伤后 6 小时和 24 小时评估后肢运动功能。缺血再灌注损伤后 24 小时取出脊髓,进行组织学和免疫组织化学分析及实时聚合酶链反应评估。

结果

MSC 和 PBS 组大鼠术后出现弛缓性轻瘫/截瘫。与 PBS 组相比,MSC 组在缺血再灌注损伤后 6 小时和 24 小时后后肢功能明显更好(p < 0.05)。脊髓中末端脱氧核苷酸转移酶 dUTP 缺口末端标记阳性神经元细胞的数量和 Bax 与 Bcl2 的比值在 PBS 组明显更大(p < 0.05)。缺血再灌注损伤后 24 小时在脊髓中观察到注入的 MSCs。

结论

脊髓缺血再灌注损伤后立即通过动脉内注射 MSC 治疗可能通过防止脊髓神经元细胞凋亡来改善下肢功能。

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