摘要
目的研究粒细胞集落刺激因子(G-CSF)对大鼠脑出血(ICH)后脑水肿和星型胶质细胞可塑性的影响及神经保护作用。方法 SD大鼠随机分为假手术组、模型组、治疗组。断尾取自体血法制备大鼠ICH模型,治疗组于造模1h后腹腔注射重组粒细胞集落刺激因子(rhG-CSF)60μg/kg。3组大鼠于术后6h、24h、48h、72h、7d、10d处死,干湿重法测定脑组织含水量、免疫组化检测血肿周围MMP-9、GFAP的动态变化。结果模型组脑组织含水量明显高于假手术组(P<0.05),造模后48h、72h最明显,与组内6h、24h、7d、10d相比差异显著(P<0.05);治疗组脑组织含水量明显低于模型组(P<0.05)。模型组各时点MMP-9表达明显高于假手术组(P<0.05),48h、72h表达最明显,与组内6h、24h、7d、10d比较差异显著(P<0.05);治疗组各时点MMP-9表达显著低于模型组(P<0.05)。假手术组脑组织含水量与MMP-9表达无相关性(r=0.429,P>0.05),模型组脑组织含水量与MMP-9表达呈正相关关系(r=0.922,P<0.05),治疗组脑组织含水量与MMP-9表达呈正相关关系(r=0.844,P<0.05)。假手术组未见GFAP阳性细胞表达;模型组6h出现少量GFAP阳性细胞表达,48h增多,72h大量表达,7d达高峰,10d表达减弱;治疗组GFAP阳性细胞表达6h与模型组相似,24h、48h、72h、7d、10d较模型组明显减少(P<0.05)。结论 ICH后G-CSF可抑制MMP-9表达减轻脑水肿程度,抑制星形胶质细胞过度活化,对出血后脑组织具有保护作用。
Objective To explore the neuroprotective effects of granulocyte colony-stimulating factor（G-CSF）in intracerebral hemorrhage（ICH）rats following the changes of brain edema and astrocytes plasticity in this study.Methods Sprague-Dawley rats were randomly divided into three groups：the sham operation group,the model group,the treating group.According to rat brain stereotaxic atlas,we made model of ICH by the method cutting off tail of rat to obtain blood.The treating group was administered rhG-CSF（60μg/kg）intraperitonealy 1h after operation.The brain edema was measured by dry-wet weigh method,MMP-9 and GFAP were measured by immunohistochemical method in every group post operation 6h、24h、48h、72h、7d、10d.Results The brain edema of the model group were markedly higher than the sham operation group（P〈0.05）,reaching the peak at 48h、72h and the difference was significant inwith 6h、24h、7d、10d（P〈0.05）.The brain edema of the treating group wasere significantly decreased than the model group（P〈0.05）.The contents of MMP-9 protein were higher in the model group than in the sham operation group（P〈0.05）.MMP-9 reached the peak at 48h and 72h in the model group,and there were significant difference compared to at 6h、24h、7d and 10d（P〈0.05）.The contents of MMP-9 protein were significantly lower in the treating group than in the model group in each time point（P〈0.05）.In the sham operation group,the changes of the contents of MMP-9 protein were negatively correlated with the brain edema（r=0.429,P〈0.05）.In the model group,the changes of the contents of MMP-9 protein were positively correlated with the brain edema（r=0.922,P〈0.05）.In the treating group,the changes of the contents of MMP-9 protein were positively correlated with the brain edema（r=0.844,P〈0.05）.There was not GFAP-positive cell found in the sham operation group.In the model group,the GFAP was little expressed at 6h,increased at 48h,there were large numbers of GFAP-positive cells at 72h,reached a peak at 7d,then decreased at 10d.The expression of GFAP in the experimental group was identical to that of the model group at 6h;however,the number of GFAP-positive cells was obvious decreased than the model group at 24h、48h、72h、7d and 10d after intervention（P〈0.05）.Conclusion G-CSF can downregulate MMP-9 expression to decrease the brain edema and inhibit the activation of astrocytes,which may be play an important role in the process of protection process inof the nerve tissues after intracerebral hemorrhage.
出处
《中风与神经疾病杂志》
CAS
CSCD
北大核心
2013年第5期404-408,共5页
Journal of Apoplexy and Nervous Diseases
基金
四川省卫生厅资助项目(编号110368)
泸州市科技局资助项目(编号2011001)
关键词
粒细胞集落刺激因子
脑出血
脑水肿
基质金属蛋白酶-9
胶质纤维酸性蛋白
Granulocyte colony-stimulating factor
Intracerebral hemorrhage
Brain edema
Matrix metalloproteinases-9
Glial fibrillary acidic protein
