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粒细胞集落刺激因子对脑出血大鼠的治疗机制

     

摘要

Objective To explore the effects of granulocyte colony-stimulating factor ( G-CSF) on brain edema and astrocytes plas-ticity in a rat model of intracerebral hemorrhage ( ICH).Methods Experimental ICH model was induced by right caudate nucleus adminis-tration 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 pro-tein 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 activa-tion of astrocytes.%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。

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