自体骨髓干细胞动员联合辛伐他汀治疗脑出血的实验研究  

Therapeutic effects of combination autologous bone marrow stem cells mobilization and simvastatin on intracerebral hemorrhage in rats

作　　者：郭晓鹤[1] 步星耀[1] 姜金豆[1] 程培训[1] 闫兆月[1] 

机构地区：[1]河南省人民医院神经外科,郑州450053

出　　处：《中华临床医师杂志（电子版）》2011年第24期7248-7255,共8页Chinese Journal of Clinicians(Electronic Edition)

摘　　要：目的探讨自体骨髓干细胞(BMSCs)动员联合辛伐他汀治疗脑出血的疗效、机制。方法选用成年SD大鼠制备脑出血动物模型,随机分为对照组、辛伐他汀治疗组、自体BMSCs动员组和自体BMSCs动员联合辛伐他汀组。采用改良神经功能缺损程度评分(mNSS)检测大鼠脑功能,组织病理和免疫荧光双标及免疫组织化学检测BrdU/GFAP、BrdU/NSE及Nestin、BDNF和Ⅷ因子抗原,TUNEL检测细胞凋亡。结果脑出血4周时,自体BMSCs动员联合辛伐他汀组mNSS评分明显低于辛伐他汀治疗组和自体BMSCs动员组,后两组均显著低于对照组;脑组织病理显示炎症水肿、缺血由重至轻依次为对照组、辛伐他汀治疗组、自体BMSCs动员组和自体BMSCs动员联合辛伐他汀组;自体BMSCs动员联合辛伐他汀组BrdU/GFAP和BrdU/NSE免疫荧光双标阳性细胞数显著高于辛伐他汀治疗组(P1=0.000,P2=0.000)和自体BMSCs动员组(P1=0.000,P2=0.000),后两组均显著高于对照组(P1=0.000,P2=0.000);自体BMSCs动员联合辛伐他汀组Nestin和Ⅷ因子阳性表达数分别显著高于辛伐他汀治疗组(P1=0.000,P2=0.000)和自体BMSCs动员组(P1=0.000,P2=0.000),后两组均显著高于对照组(P1=0.000,P2=0.000)。自体BMSCs动员联合辛伐他汀组BD-NF阳性表达数与自体BMSCs动员组相比较差异无统计学意义(P=0.225),但显著高于辛伐他汀组(P=0.005),后两组均显著高于对照组(P1=0.000,P2=0.000);自体BMSCs动员联合辛伐他汀组细胞凋亡数明显低于辛伐他汀治疗组(P=0.000)和自体BMSCs动员组(P=0.000),后两组均显著低于对照组(P1=0.000,P2=0.000)。结论自体BMSCs动员联合辛伐他汀可协同促进BMSCs向出血区脑组织聚集、增殖、分化,分泌神经营养因子、促进血管生成、减少细胞凋亡,增强脑出血后神经再生与脑损伤的修复,明显改善脑出血大鼠脑功能。Objective To explore the efficacy and the mechanism of autologous bone marrow stem cells (BMSCs) mobilization combined with simvastatin in the treatment of intracerebral hemorrhage(ICH).Methods Primary ICH were induced in adult Sprague-Dawley rats,then the animals were randomly assigned to PBS control,simvastatin monotherapy,BMSCs monotherapy,or combination therapy group of BMSCs mobilization and simvastatin.Modified neurological severity score were done in all rats to measure the function of the nervous system.Histopathology observation,immunofluorescence staining and immunohistochemistry were performed respectively to detect BrdU/GFAP,BrdU/NSE,BDNF,Nestin and FactorⅧ antigen after the cerebral tissue were taken out.Cell apoptosis was detected by TUNEL.Results The mNSS were significantly lower in combination therapy group of BMSCs mobilization and simvastatin compared with the simvastatin monotherapy or BMSCs monotherapy group at 4 weeks,and the PBS control group was higher than the other two monotherapy groups respectively.Histopathology of the brain demonstrated that the inflammation,edema and ischemia was the smallest respectively in combination therapy group of BMSCs mobilization and simvastatin,follwed by BMSCs monotherapy,simvastatin monotherapy and PBS control group.At 4 weeks post-ICH,the number of BrdU/GFAP and BrdU/NSE double positive cells were significantly higher respectively in combination therapy group of BMSCs mobilization and simvastatin compared with the simvastatin monotherapy (P1=0.000,P2=0.000)or BMSCs monotherapy group(P1=0.000,P2=0.000),and the PBS control group was lower than the other two monotherapy groups respectively(P<0.05).The expression of Nestin and FactorⅧ were much higher in combination therapy group of BMSCs mobilization and simvastatin than in the monotherapy or BMSCs monotherapy group(P1=0.000,P2=0.000),and PBS control group was lower than the other two monotherapy groups respectively(P1=0.000,P2=0.000).The expression of BDNF was higher in combination therapy group of BMS

关 键 词：脑出血 骨髓祖代细胞 动员 辛伐他汀 

分 类 号：R743.34[医药卫生—神经病学与精神病学]