NT-3 通过 MAPK 信号通路对脊髓损伤修复的影响。
Effect of NT-3 on repair of spinal cord injury through the MAPK signaling pathway.
机构信息
Department of Orthopedics, Xinghua People's Hospital, Xinghua, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2165-2172. doi: 10.26355/eurrev_202003_20481.
OBJECTIVE
The aim of this study was to explore the effect of neurotrophin-3 (NT-3) on the repair of spinal cord injury (SCI) through the mitogen-activated protein kinase (MAPK) signaling pathway.
MATERIALS AND METHODS
The rat model of SCI was first successfully established using the impactor (SCI group). Meanwhile, control group and NT-3 treatment group were set up as well. Basso-Beattie-Bresnahan (BBB) score was given and blood, and spinal cord tissues were collected from rats. Subsequently, serum indexes were detected, including glucose (Glu), creatinine (Cr), K+, Na+, the content of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-β (TNF-β), and the level of myeloperoxidase (MPO). Moreover, the morphological changes were observed via hematoxylin-eosin (HE) staining. The gene and protein expressions of glial fibrillary acidic protein (GFAP) and MAPK were determined through Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting, respectively. Furthermore, the effect of the MAPK signaling pathway on SCI was comprehensively observed.
RESULTS
In SCI group, the rats could not crawl autonomously with the loss of motor function and paraplegia. Meanwhile, the levels of Glu, Cr, Na+, IL-6, IL-1β, TNF-β, and MPO were all significantly up-regulated. According to the results of HE staining, spinal nerve fibers disappeared with significant syringomyelia in SCI group. Meanwhile, the aggregation of nerve fibers was observed without apparent tissue bleeding, edema, and cell deformation in NT-3 group. QRT-PCR results demonstrated that SCI group showed remarkably higher levels of GFAP, MAPK, and c-Jun N-terminal kinase (JNK) (p<0.05), while it showed a markedly lower level of ERK2 than NT-3 group (p<0.05). In NT-3 group, the protein expression of MAPK in myocardial tissues was remarkably lower than that of SCI group (p<0.05).
CONCLUSIONS
NT-3 can inhibit the MAPK signaling pathway, thereby promoting the repair of SCI.
目的
本研究旨在探讨神经营养因子-3（NT-3）通过丝裂原活化蛋白激酶（MAPK）信号通路对脊髓损伤（SCI）修复的影响。
材料和方法
首先采用撞击器成功建立大鼠 SCI 模型（SCI 组），同时设立对照组和 NT-3 治疗组。对大鼠进行巴索-比蒂-布雷森汉（BBB）评分，并采集血液和脊髓组织。随后检测血清指标，包括葡萄糖（Glu）、肌酐（Cr）、K+、Na+、白细胞介素-6（IL-6）、IL-1β、肿瘤坏死因子-β（TNF-β）和髓过氧化物酶（MPO）的含量。此外，通过苏木精-伊红（HE）染色观察形态学变化。采用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法（Western blot）分别检测神经胶质纤维酸性蛋白（GFAP）和 MAPK 的基因和蛋白表达。进一步综合观察 MAPK 信号通路对 SCI 的影响。
结果
SCI 组大鼠运动功能丧失，出现截瘫，不能自主爬行。同时，Glu、Cr、Na+、IL-6、IL-1β、TNF-β和 MPO 水平均显著升高。HE 染色结果显示，SCI 组脊髓神经纤维消失，出现明显的空洞症。而 NT-3 组神经纤维聚集，未见明显组织出血、水肿和细胞变形。实时荧光定量 PCR 结果显示，SCI 组 GFAP、MAPK 和 c-Jun N-末端激酶（JNK）表达水平显著升高（p<0.05），而 ERK2 表达水平显著降低（p<0.05）。NT-3 组 MAPK 蛋白在心肌组织中的表达明显低于 SCI 组（p<0.05）。
结论
NT-3 可抑制 MAPK 信号通路，从而促进 SCI 的修复。
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