重庆医学2025，Vol.54Issue(11)：2522-2527,6.DOI:10.3969/j.issn.1671-8348.2025.11.008
外源性Nogo受体拮抗剂通过影响轴突再生促进脊髓损伤大鼠神经功能恢复的机制研究
Mechanism study of exogenous Nogo receptor antagonists promote the recovery of neural function in rats with spinal cord injury through affecting axon regeneration
摘要
Abstract
Objective To investigate the effect of the Nogo receptor antagonist NEP1-40,administered via an exogenous route,on axonal regeneration in rats with spinal cord injury(SCI),and to explore its mecha-nism of action in the process of neural repair.Methods SD rats were divided into a sham surgery group(Group A),an injury group(Group B),and an injury+NEP1-40 treatment group(Group C).In Group A,only laminectomy was performed without spinal cord injury.Groups B and C were subjected to a clip-type SCI model.Group C received treatment with NEP1-40 based on the established SCI model.Hindlimb motor func-tion in the three groups was assessed using the BBB score at 1,3,7,and 14 days post-surgery.Real-time quan-titative PCR(qPCR)and Western blot were used to detect changes in gene and protein expression levels of growth-associated protein-43(GAP-43)and microtubule-associated protein-2(MAP-2),characteristic markers of axonal and dendritic regeneration.Immunofluorescence was employed to analyze NF-200 and BrdU double-labeling,and changes in the number of double-labeled positive cells were observed and analyzed.Results In group A rats,the BBB scores at various time points after surgery showed no significant change compared with preoperative scores.In groups B and C,the BBB scores on postoperative day 1 were obviously lower than pre-operative scores.From days 3 to 14 after surgery,the BBB scores partially recovered compared with postopera-tive day 1,though they remained lower than those in group A.However,on postoperative days 3,7,and 14,the BBB scores in group C were higher than those in group B(P<0.05).qPCR and Western blot results showed that compared with preoperative levels,GAP-43 and MAP-2 mRNA and protein expression in groups B and C at postoperative days 3,7,and 14 showed a trend of first decreasing and then increasing,and the expression in group C was consistently higher than in group B(P<0.05).The expression level of NogoA in group C showed an opposite trend to GAP-43 and MAP-2.Compared with preoperative levels,NogoA mRNA and pro-tein expression in group B rats decreased on postoperative days 1 and 3(P<0.05)and increased on days 7 and 14(P<0.05).Compared with preoperative levels,NogoA mRNA and protein expression in groups B and C also showed a trend of first decreasing and then increasing,but in group C,at all postoperative time points except day 1,it was lower than in group B(P<0.05).Immunofluorescence results showed that over time,the number of cells double-labeled with BrdU and NF-200 gradually increased,with the highest number observed in group C on postoperative day 14.Conclusion NEP1-40 promotes neurological repair in SCI,providing a new approach for SCI repair treatment.关键词
脊髓损伤/Nogo受体拮抗剂/生长相关蛋白-43/微管相关蛋白-2Key words
spinal cord injury/Nogo receptor antagonist/growth-associated protein 43/microtubule-as-sociated protein 2分类
医药卫生引用本文复制引用
李贺祥,王春庆,李青,罗奕,曾佳学..外源性Nogo受体拮抗剂通过影响轴突再生促进脊髓损伤大鼠神经功能恢复的机制研究[J].重庆医学,2025,54(11):2522-2527,6.基金项目
国家自然科学基金项目(82160249). （82160249）
