Effect of montelukast combined with bone marrow mesenchymal stem cell transplantation on spinal cord injury in rat models

doi:10.12307/2021.005

Abstract

Abstract: BACKGROUND: Combination with a variety of treatment methods can effectively intervene for different targets, play a synergistic or superimposed effect, and has become a new concept of clinical treatment of spinal cord injury.
OBJECTIVE: To investigate the effect of montelukast combined with bone marrow mesenchymal stem cell transplantation on the recovery of neurological function in rats with spinal cord injury.
METHODS: Sixty 8-week-old healthy male Sprague-Dawley rats were randomly divided into four groups, each with 15 rats, namely model group, montelukast group, bone marrow mesenchymal stem cell group, and combination group. The spinal cord injury model was performed in each group according to the Allen method, and montelukast 5 mg/kg or the equivalent amount of normal saline was administered by gavage at 1 and 6 hours after the model was successfully established, and then once a day for 30 days. At 2 hours after modeling, 1 μL of BrdU-labeled bone marrow mesenchymal stem cell suspension or an equivalent amount of PBS was injected into the spinal cord injury area at a time. At 1, 3, 7, 14, 21, and 30 days after modeling, the BBB score and Rivlin inclined plate test were used to evaluate the motor function of the rat’s hind limbs. At 7 days after modeling, the histopathological changes of spinal cord were observed by hematoxylin-eosin staining and Nissl staining. Immunohistochemical method was applied to detect the expression of glial fibrillary acidic protein, interleukin-1β and BrdU positive labeling rate in rat spinal cord tissue. Western blot assay was used to detect the expression of apoptosis-related proteins Bcl-2, Bax and Caspase-3 in rat spinal cord tissue.
RESULTS AND CONCLUSION: (1) At 7, 14, 21, and 30 days after modeling, the BBB score and Rivlin inclined plate test results of the combination group, montelukast group and bone marrow mesenchymal stem cell group were significantly higher than those of the model group (P < 0.05). (2) At 7 days, , the inflammatory reaction and edema were reduced; the area of injury cavity and glial scar was reduced; and the structure of damaged segment was improved in combination group, montelukast group and bone marrow mesenchymal stem cell group. (3) At 7 days, the expressions of glial fibrillary acidic protein and interleukin-1β in combination group, montelukast group and bone marrow mesenchymal stem cell group were significantly lower than those in the model group (P < 0.05). The positive rate of BrdU in combination group was higher than that in bone marrow mesenchymal stem cell group (P=0.000). (4) At 7 days, the expression levels of Bax and Caspase-3 in combination group, montelukast group and bone marrow mesenchymal stem cell group were significantly lower than those in the model group (P < 0.05); the expression of Bcl-2 was significantly higher than that in the model group (P < 0.05). (5) All the above indexes in combination group were better than those in montelukast group and bone marrow mesenchymal stem cell group. (6) The results show that montelukast combined with bone marrow mesenchymal stem cells transplantation can significantly improve the neuromotor function of rats after spinal cord injury. The mechanism may be related to inhibiting local inflammatory response and glial cell proliferation, reducing the expression of apoptosis-related proteins, and increasing the survival rate of bone marrow mesenchymal stem cell transplantation.

Key words: stem cells, bone marrow mesenchymal stem cells, spinal cord injury, montelukast, glial fibrillary acidic protein, interleukin-1β, BrdU staining

CLC Number:

Sun Jianwei, Yang Xinming, Zhang Ying. Effect of montelukast combined with bone marrow mesenchymal stem cell transplantation on spinal cord injury in rat models[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(25): 3962-3969.

Figures/Tables 8

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