中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (7): 1273-1280.doi: 10.4103/1673-5374.301485

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

免疫调节肽对脊髓损伤的神经保护

  

  • 出版日期:2021-07-15 发布日期:2021-01-07
  • 基金资助:

    墨西哥塞古罗社会研究所(IMSS)的研究基金会和Consejo Nacional de Ciencia yTecnología(CONACYT)奖学金资助

Neuroprotective effect of immunomodulatory peptides in rats with traumatic spinal cord injury

Dulce Parra-Villamar1, Liliana Blancas-Espinoza1, Elisa Garcia-Vences2, 3, Juan Herrera-García1, Adrian Flores-Romero2, 3, Alberto Toscano-Zapien1, Jonathan Vilchis Villa1, Rodríguez Barrera-Roxana2, 3, Soria Zavala Karla1, 2, Antonio Ibarra2, 3, *, Raúl Silva-García1, *   

  1. 1 Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI; Instituto Mexicano del Seguro Social; Ciudad de México, México;  2 Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México, Campus Norte, Huixquilucan, Edo de México, México;  3 Centro de Investigación del Proyecto Camina A.C, Ciudad de México, México 
  • Online:2021-07-15 Published:2021-01-07
  • Contact: Antonio Ibarra, MD, MSc, DSc, jose.ibarra@anahuac.mx; Raúl Silva-García, MSc, DSc, silgarrul@yahoo.com.mx.
  • Supported by:
    This study was supported by Fondo de Investigación en Salud of the Instituto Mexicano del Seguro Social (IMSS), under the support No. FIS/IMSS/PROT/G17/1676 and FIS/IMSS/PROT/G18/1825 and the scholarship granted to the students of Master’s degree by Consejo Nacional de Ciencia y Tecnología (CONACYT) and IMSS.

摘要:

目前临床上用于脊髓损伤的治疗方法均未取得十分令人满意的效果。已有研究免疫调节肽单核细胞运动抑制因子(MLIF),A91肽和谷胱甘肽单乙酯(GSH-MEE)单独应用对脊髓损伤大鼠运动恢复的促进作用;为评估3种免疫调节肽组合对慢性期脊髓损伤的影响,实验对雌性脊髓损伤大鼠进行了T9椎板椎板切除,以建立中度挫伤脊髓损伤模型。伤后2个月,旷场试验显示免疫调节肽组合干预的脊髓损伤大鼠运动功能明显恢复。HE,Luxol Fast Blue,免疫组化及Masson染色显示,免疫调节肽组合干预的脊髓损伤大鼠脊髓实质组织和白质保留、脊髓运动神经元和轴突纤维数量均明显增加。免疫调节肽组合疗法可保持脊髓损伤大鼠脊髓组织的完整性,并改善其运动功能。

https://orcid.org/0000-0003-2489-4689 (Antonio Ibarra); 

https://orcid.org/0000-0002-6178-9063 (Raúl Silva-García)

Abstract: Several therapies have shown obvious effects on structural conservation contributing to motor functional recovery after spinal cord injury (SCI). Nevertheless, neither strategy has achieved a convincing effect. We purposed a combined therapy of immunomodulatory peptides that individually have shown significant effects on motor functional recovery in rats with SCI. The objective of this study was to investigate the effects of the combined therapy of monocyte locomotion inhibitor factor (MLIF), A91 peptide, and glutathione monoethyl ester (GSH-MEE) on chronic-stage spinal cord injury. Female Sprague-Dawley rats underwent a laminectomy of the T9 vertebra and a moderate contusion. Six groups were included: sham, PBS, MLIF + A91, MLIF + GSH-MEE, A91 + GSH-MEE, and MLIF + A91 + GSH-MEE. Two months after injury, motor functional recovery was evaluated using the open field test. Parenchyma and white matter preservation was evaluated using hematoxylin & eosin staining and Luxol Fast Blue staining, respectively. The number of motoneurons in the ventral horn and the number of axonal fibers were determined using hematoxylin & eosin staining and immunohistochemistry, respectively. Collagen deposition was evaluated using Masson’s trichrome staining. The combined therapy of MLIF, A91, and GSH-MEE greatly contributed to motor functional recovery and preservation of the medullary parenchyma, white matter, motoneurons, and axonal fibres, and reduced the deposition of collagen in the lesioned area. The combined therapy of MLIF, A91, and GSH-MEE preserved spinal cord tissue integrity and promoted motor functional recovery of rats after SCI. This study was approved by the National Commission for Scientific Research on Bioethics and Biosafety of the Instituto Mexicano del Seguro Social under registration number R-2015-785-116 (approval date November 30, 2015) and R-2017-3603-33 (approval date June 5, 2017). 

Key words: glutathione monoethyl ester, monocyte locomotion inhibitor factor, motor functional recovery, neuroprotection, neurorestoration, peptides, protective autoimmunity, spinal cord injury