盐酸西妥昔德通过抑制炎症和延长神经元的存活,促进脊髓损伤的恢复。
Cinepazide maleate promotes recovery from spinal cord injury by inhibiting inflammation and prolonging neuronal survival.
发表日期:2023 Mar 29
作者:
Dadi Li, Shuxian Zhao, Bin Zhu, Wanmin Zhao, Ya Ding, Xuejun Li, Donglin Fu, Haiyang Yu, Baogui Wang, Tan Pan
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
本研究旨在探讨环丙嗪酸盐(CM)对大鼠脊髓损伤(SCI)的治疗作用,为CM作为SCI的预防和治疗策略提供实验基础。末端脱氧核苷酸转移酶dUTP尾端标记染色和蛋白质印迹分析用于评估神经细胞凋亡。酶联免疫吸附法用于分析脊髓组织和脑脊液中白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α(TNF-α)的表达。CD68染色和蛋白质印迹分析用于研究CM对微胶质细胞活化的影响。Basso-Beattie-Bresnahan(BBB)评分、足印测定、苏木精-伊红染色和神经元核(NeuN)染色用于研究SCI后CM对大鼠运动功能和组织学损伤的影响。开发了神经元细胞损伤和微胶质细胞炎症的体外模型,研究了CM对凋亡和炎症的影响。功能测试(BBB评分和足印测试)表明,CM治疗组的大鼠运动功能显著改善。体内CM治疗减少了损伤部位凋亡细胞的数量。同样,体外CM治疗减少了H2O2诱导的神经元凋亡。体内CM治疗减少了CD68阳性微胶质细胞的数量和TNF-α、IL-1β和IL-6的表达水平。同样,体外CM治疗减少了LPS诱导的微胶质细胞促炎细胞因子。CM通过抑制SCI引起的凋亡和炎症反应,减少大鼠SCI后腔的面积,促进运动功能的恢复。这些发现表明CM是SCI治疗中值得研究的潜在药物。©2023 Wiley Periodicals LLC.
This study aimed to investigate the therapeutic effects of cinepazide maleate (CM) on spinal cord injury (SCI) in rats, thereby providing an experimental basis for the use of CM as a preventative and therapeutic strategy for SCI. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining and western blot analysis were used to assess neural cell apoptosis. enzyme-linked immunosorbent assay was used to analyze the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in spinal cord tissues and cerebrospinal fluid. CD68 staining and western blot analysis were used to investigate the effect of CM on microglia activation. The effects of CM on motor function and histological damage in rats after SCI were investigated using the Basso-Beattie-Bresnahan (BBB) score, footprint assay, hematoxylin and eosin staining, and NeuN staining. In vitro models of neuronal cell injury and microglial inflammation were developed to investigate the effects of CM on apoptosis and inflammation. Functional tests (BBB score and footprint test) revealed that CM-treated rats had significantly improved motor function. In vivo CM treatment reduced the number of apoptotic cells at the site of injury. Similarly, in vitro CM treatment reduced H2 O2 -induced neuronal apoptosis. In vivo CM treatment reduced the number of CD68-positive microglia and the expression levels of TNF-α, IL-1β, and IL-6. Similarly, in vitro CM treatment reduced LPS-induced pro-inflammatory cytokines in microglia. CM promotes the recovery of motor function by inhibiting SCI-induced apoptosis and inflammatory responses and reducing the area of the post-SCI cavity in rats. These findings indicate that CM is a potential drug worthy of translational studies for SCI treatment.© 2023 Wiley Periodicals LLC.