摘要
目的了解雄激素对创伤性脑损伤(TBI)大鼠脑组织磷酸蛋白聚糖(PC)及NG2蛋白聚糖表达影响及其与TBI后神经修复的关系,探讨其神经保护及再生的作用机制。方法制作大鼠TBI模型,随机分为正常组、TBI模型组、雄激素干预组(于模型制成后即刻注射丙酸睾丸酮注射液25 mg/kg)。造模后1、3、5、7 d取脑组织制作石蜡切片和电镜切片,用免疫组织化学法观察PC和NG2在损伤区表达的动态变化,应用透射电镜对比观察损伤区及其周围的神经元超微结构变化、细胞损伤、凋亡、神经元轴突再生及胶质细胞增生情况。结果①TBI模型组造模后1 d可见脑细胞肿胀、凋亡,3、7 d细胞水肿,可见凋亡细胞、胶质细胞于损伤外围增生;雄激素干预组1、3、5和7 d时细胞水肿,可见凋亡细胞、损伤外围胶质细胞增生情况明显降低,TBI模型组细胞表面无突起或仅有较小突起;雄激素干预组的神经元轴突较TBI模型组增长明显。②造模后脑组织PC和NG2的表达:正常组脑组织均存在少量PC和NG2的表达;TBI模型组在造模后1 d表达开始呈阳性反应,造模后3 d明显增多,7 d达高峰,但仍高于正常组;雄激素干预组,PC和NG2的表达时间程度及分布与TBI模型组相似,雄激素干预组造模后1、3、5、7 d后损伤区及周围表达水平明显低于TBI模型组,差异均有统计学意义(P<0.01)。结论雄激素可通过调节胶质细胞形态结构和功能抑制PC和NG2表达促进神经元轴突再生,从而发挥神经保护。
Objective To study the effects of androgen on phosphacan （PC） and NG2 proteoglycan （NG2） ex-pression and neuronal regeneration in traumatic brain injury （TBI） rat models, thus unraveling the potential mecha-nisms underlying the protective effects of androgen against TBI. Methods Following construction of TBI models, the rats were randomly assigned to normal control group, TBI group and androgen treatment group. Rats in the androgen treatment group were subject to testosterone propionate （25 mg/kg） injection immediately after TBI. The cerebral tis-sues were extracted at 1 d, 3 d, 5 d and 7 d for preparation paraffin sections and electron microscopy section. Im-munohistochemistry assay was employed to assess the dynamic changes in phosphacan and NG2 expression in the in-jured area. Transmission electron microscopy was applied to detect the ultrastructure, cell injury, apoptosis, neuronal axial regeneration and neuroglia regeneration. Results In TBI model group, neuronal cell enlargement and apoptosis could be observed at 1 d, and neuronal cell swelling, apoptosis and neuroglia regeneration was seen at 3 d and 7 d. In the androgen treatment group, the cell apoptosis and neuroglia regeneration were suppressed except that cell swelling could be observed at 1 d, 3 d, 5 d and 7 d. The TBI group was characterized by nil or minor processes on the surface of neurons, whilst androgen resulted in marked growth of neuronal processes. In normal control group, PC and NG2 were scarcely expressed. However, TBI was associated with notable PC and NG2 expression at 1 d, which gradually increased at 3 d and culminated at 7 d. Despite a similar pattern of the time-dependent growth and distribution, an-drogen treatment yielded significantly attenuated PC and NG2 expression at 1 d, 3 d, 5 d and 7 d compared TBI group （all P〈0.01）. Conclusion The neuroprotection effects of androgen against TBI is associated with the regulation of neuroglia morphology and inhibition of PC and NG2 expression leading to neuronal axial
出处
《中国药物与临床》
CAS
2014年第5期594-596,I0001,共4页
Chinese Remedies & Clinics
关键词
脑损伤
雄激素类
蛋白聚糖类
轴突
再生
大鼠
Brain injuries
Androgens
Proteoglycans
Axons
Regeneration
Rats
