【摘要】 目的探讨粒细胞集落刺激因子(C-CSF)对大鼠脑出血后脑组织水肿、基质金属蛋白酶-9(MMP-9)、星型胶质细胞活性(Ast)的影响。方法 SD大鼠96只,随机分为假手术组、脑出血组、治疗组。治疗组造模1 h后腹腔注射重组C-CSF,三组大鼠分别于术后6 h、24 h、48 h、72 h、7 d、10 d处死,测定脑组织含水率、血肿周围MMP-9、胶质生蛋白(GFAP)的表达。结果假手术组无明显脑水肿,脑出血组脑组织含水率明显增加,并于48~72 h达高峰,治疗组各时间点脑组织含水率和脑出血组相比明显减轻(P<0.05)。假手术组MMP-9仅有少量表达,脑出血组MMP-9表达明显增加,48~72 h达高峰,治疗组各时间点MMP-9表达与脑出血组相比明显减轻(P<0.05)。假手术组脑组织含水率与MMP-9表达无相关性(r=0.429,P>0.05),脑出血组脑组织含水率与MMP-9表达呈正相关关系(r=0.922,P<0.05),治疗组脑组织含水率与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;脑出血组6 h出现少量GFAP阳性细胞表达,48 h增多,72 h大量表达,7 d达高峰,10 d表达减弱;治疗组GFAP阳性细胞表达6 h与脑出血组相似,24 h、48 h、72 h、7 d、10 d较脑出血组明显减少(P<0.05)。结论 C-CSF能明显减轻脑水肿、降低基质MMP-9表达和Ast过度活化引起的脑损伤,保护大脑神经功能。更多还原

【Abstract】 Objective To explore the effects of granulocyte colony-stimulating factor( G-CSF) on brain edema and astrocytes plasticity in a rat model of intracerebral hemorrhage( ICH). Methods Experimental ICH model was induced by right caudate nucleus administration of autologous whole blood in SD rat. The rats were randomly divided into sham,ICH and G-CSF treatment groups. Rats in treatment group were administered rhG-CSF( 60 μg / kg) by intraperitoneal injection post operation 1 h. The brain edema was measured by dry-wet weigh method,matrix metalloproteinase( MMP)-9 and glial fibrillary acidic protein( GFAP) were measured by immunohistochemical method in every group post operation 6 h,24 h,48 h,72 h,7 d,10 d. Results The contents of brain edema in ICH group were strong,reaching the peak at 48 h ~ 72 h,and its expression in sham group which was dark( P<0. 05). In treatment group,the contents of brain edema were significantly decreased at each time-point compared to ICH group( P<0. 05). The expressions of MMP-9 in ICH group were strong,reaching the peak at 48 h ~ 72 h,and its expression in sham operation group was dark( P<0. 05). In treatment group,the expressions of MMP-9 were significantly decreased at each time-point compared to ICH group( P<0. 05). In the sham 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 ICH 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 treatment 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 group. In the ICH group,the GFAP was little expressed at 6 h,and then was increased gradually,there were large numbers of GFAP-positive cells at 72 h, reached a peak at 7 d,then decreased at 10 d. The expression of GFAP in the treatment group was identical to that of the ICH group at 6 h. However,the number of GFAP-positive cells was obvious decreased than that of ICH group at 24 h,48 h,72 h,7 d and 10 d after treatment( P<0. 05). Conclusions G-CSF plays a therapeutic effect on ICH by inhibiting the expression of MMP-9 and down-regulating the activation of astrocytes.更多还原