摘要
目的探讨在大鼠脊髓损伤(SCI)后胶质瘢痕形成早期,p38丝裂原活化蛋白激酶(P38 MAPK)对神经胶质纤维酸性蛋白(GFAP)及波形蛋白(vimentin)表达的影响。方法将大鼠随机分为假手术组(sham group)、模型组(model group)、P38 MAPK特异性激动剂anisomycin组(anisomycin group)和P38 MAPK特异性抑制剂SB203580组(SB203580group)。脊髓夹伤模型制作成功后即分别在损伤区硬脊膜下注射0.9%氯化钠溶液、anisomycin和SB203580各10μL,假手术组只打开椎板暴露脊髓,不做其他处理。于术后第1、3、7及14天利用BBB评分评定大鼠后肢运动功能,用Western blot和免疫荧光标记技术检测GFAP和vimentin表达。结果术后第14天,模型组BBB评分显著低于假手术组(P<0.01);SB203580组大鼠BBB评分显著高于模型组(P<0.05)但仍低于假手术组(P<0.01),而anisomycin组则显著低于模型组(P<0.05)。术后第7和14天,模型组GFAP、vimentin的表达显著高于假手术组(P<0.01);SB203580组GFAP、vimentin的表达均显著低于模型组(P<0.05)但仍高于假手术组(P<0.05),而anisomycin组GFAP、vimentin的表达均显著高于模型组(P<0.05)。结论 SCI后胶质瘢痕形成早期P38 MAPK可调控GFAP、vimentin的表达,抑制P38 MAPK可降低GFAP、vimentin的表达,减轻大鼠SCI后胶质瘢痕形成,促进神经功能的恢复。
Objective To explore p38 mitogen-activated protein kinase（ P38 MAPK） regulating glial fibrillary acidic protein（ GFAP） and vimentin expressions at the early stage of glia scar formation after spinal cord injury in rats.Methods Rats were divided into sham group,model group,P38 MAPK specific agonists group（ anisomycin group） and P38 MAPK specific inhibitor group（ SB203580 group） randomly. Normal saline（ model group）,P38 MAPK agonist anisomycin（ anisomycin group）,P38 MAPK inhibitor SB203580（ SB203580 group） every 10 μL were respectively injected in the damaged area under spinal dura mater after the experimental model of SCI were created by extradural compression of the spinal cord using an aneurysm clip,and the sham group rats underwent laminectomy without SCI. The hind legs movement function of rats was evaluated by BBB scale on the 1st,3rd,7th and14 th day after SCI,and the the expressions of GFAP and vimentin were detected by western blotting and immunofluorescence assay. Results On the 14 th day after SCI,the BBB score of model group was significantly lower than that of sham group（ P〈0. 01）. the BBB score of SB203580 group was significantly higher than that of model group（ P〈0. 05）,but was still lower than that of sham group（ P〈0. 01）,and the BBB score of anisomycin group was significantly lower than that of model group（ P〈0. 05）. On the 7th and 14 th day after SCI,the expressions of GFAP and vimentin in the model group were significantly higher than that in sham group（ P〈0. 01）. the expressions of GFAP and vimentin in SB203580 group were significantly lower than that in model group（ P〈0. 05）,but were still higher than that in sham group（ P〈0. 05）,and the expresssions of GFAP and vimentin in anisomycin group were significantly higher than that in model group（ P〈0. 05）. Conclusions P38 MAPK can regulate the expression of GFAP and vimentin at the early stage of glial scar formation after SCI. Inhibition of P38 MAPK may reduce the expressions of GFAP and vimentin,lighten glial scar formation after SCI in rats and promote the recovery of neural function.
出处
《基础医学与临床》
CSCD
2016年第4期462-467,共6页
Basic and Clinical Medicine
基金
国家自然科学基金(81100906)
重庆市自然科学基金(cstc2012jj A10055)
国家临床重点专科建设经费([2011]170)
