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牛磺熊去氧胆酸可减轻神经炎症,但对脊髓损伤大鼠的长期功能恢复无支持作用。

Tauroursodeoxycholic Acid Reduces Neuroinflammation but Does Not Support Long Term Functional Recovery of Rats with Spinal Cord Injury.

作者信息

Wu Siyu, García-Rama Concepción, Romero-Ramírez Lorenzo, de Munter Johannes P J M, Wolters Erik Ch, Kramer Boris W, Mey Jörg

机构信息

Hospital Nacional de Parapléjicos, 45071 Toledo, Spain.

School of Mental Health and Neuroscience and EURON Graduate School of Neuroscience, Maastricht University, 6229 ER Maastricht, The Netherlands.

出版信息

Biomedicines. 2022 Jun 25;10(7):1501. doi: 10.3390/biomedicines10071501.

Abstract

The bile acid tauroursodeoxycholic acid (TUDCA) reduces cell death under oxidative stress and inflammation. Implants of bone marrow-derived stromal cells (bmSC) are currently under investigation in clinical trials of spinal cord injury (SCI). Since cell death of injected bmSC limits the efficacy of this treatment, the cytoprotective effect of TUDCA may enhance its benefit. We therefore studied the therapeutic effect of TUDCA and its use as a combinatorial treatment with human bmSC in a rat model of SCI. A spinal cord contusion injury was induced at thoracic level T9. Treatment consisted of i.p. injections of TUDCA alone or in combination with one injection of human bmSC into the The recovery of motor functions was assessed during a surveillance period of six weeks. Biochemical and histological analysis of spinal cord tissue confirmed the anti-inflammatory activity of TUDCA. Treatment improved the recovery of autonomic bladder control and had a positive effect on motor functions in the subacute phase, however, benefits were only transient, such that no significant differences between vehicle and TUDCA-treated animals were observed 1-6 weeks after the lesion. Combinatorial treatment with TUDCA and bmSC failed to have an additional effect compared to treatment with bmSC only. Our data do not support the use of TUDCA as a treatment of SCI.

摘要

胆汁酸牛磺熊去氧胆酸(TUDCA)可减少氧化应激和炎症状态下的细胞死亡。骨髓源性基质细胞(bmSC)植入目前正在脊髓损伤(SCI)的临床试验中接受研究。由于注射的bmSC发生细胞死亡会限制这种治疗的效果,TUDCA的细胞保护作用可能会增强其益处。因此,我们在大鼠SCI模型中研究了TUDCA的治疗效果及其作为与人bmSC联合治疗的用途。在胸段T9水平诱导脊髓挫伤损伤。治疗包括腹腔注射单独的TUDCA或与一次注射人bmSC联合使用。在六周的监测期内评估运动功能的恢复情况。脊髓组织的生化和组织学分析证实了TUDCA的抗炎活性。治疗改善了自主膀胱控制的恢复,并在亚急性期对运动功能有积极影响,然而,益处只是短暂的,以至于在损伤后1 - 6周,在使用赋形剂处理的动物和使用TUDCA处理的动物之间未观察到显著差异。与仅用bmSC治疗相比,TUDCA和bmSC联合治疗未能产生额外效果。我们的数据不支持将TUDCA用于治疗SCI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2631/9313003/7cba98a14a9f/biomedicines-10-01501-g001.jpg

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