骨髓间质干细胞对血管性痴呆大鼠BDNF和NGF的影响

Effects of intravenous administration of marrow stromal cells on expression of brain-derived neurotrophic factor and nerve growth factor in vascular dementia r ats

目的:观察静脉注射骨髓间质干细胞(marrowstromalcell,MSC)对血管性痴呆(vasculardementia,VD)大鼠脑组织脑源性神经营养因子(BDNF)和神经生长因子(NGF)表达的影响。方法:体外分离培养、扩增成年大鼠MSC。利用结扎双侧颈总动脉方法制备慢性前脑缺血动物模型,利用穿梭箱、水迷宫试验、ELISA方法检测注射MSC后30,60dVD大鼠认知功能以及脑组织BDNF和NGF含量变化。结果:与正常对照组相比,VD大鼠主动回避反应、游泳时间、错误次数和盲端时间,在造模后30和60d差异有显著性意义(P<0.01)。静脉注射MSC后30和60d,VD大鼠认知功能显著改善。造模后30,60d大鼠脑BDNF含量犤(96±27),(108±26)ng/g犦,NGF含量犤(73±22),(89±24)ng/g犦较对照组显著增高犤(51±13)ng/g,(36±11)ng/g犦,P<0.01;注射MSC后30,60d大鼠脑BDNF含量犤(180±46),(185±5)ng/g犦,NGF含量犤(115±29),(108±34)ng/g犦较模型组显著升高。结论:静脉注射MSC可显著改善VD大鼠认知功能,增加VD大鼠脑组织BDNF和NGF含量。

AIM:To observe the effects of intravenous infusion of marrow stromal cells (MS Cs) on the expressions of brain-derived neurotrophic factor (BDNF) and nerve gr owth factor (NGF) in vascular dementia (VD) rats. METHODS:Forty-four male SD rats were divided into three groups: control group (n=12),model group (n=16) and test group (n=16).The model and MSCs groups were divided into 30 and 60 d groups (n=8),respectively.MSCs isolated from adult rats were cultured and amplified in vitro.Model rats of chronic forebrain ischemia w ere subjected to permanent bilateral common carotid arteries ligation for 2 mont hs.The rats of the test group were intravenously infused with 1.2×107/mL MSCs w hich were prelabeled with Hoechst333258 in vitro at 6 hours after BCAL.Cognitive function and the contents of BDNF and NGF were observed before and at 30 and 60 d after injection of MSCs by computerized shuttle-training case, water maze te st and Enzyme-linked immunoadsorbent assay (ELISA). RESULTS:Active avoidance response, swimming time, number of errors and error t ime of VD rats at 30 and 60 d after ligation were significantly different from t hose of the normal rats (P< 0.01). Significant recovery of cognitive impairment was found in VD rats infused with MSCs after 30 and 60 d. The contents of BDNF o f the VD rats were significantly increased to (96±27) and (108±26) ng/g at 30 and 60 d after ligation, while those of NGF were significantly increased to (73 ±22) and (89±24) ng/g respectively, compared with the control group [(51±13) and(36±11)ng/g respectively, P< 0.01].The contents of BDNF in the test group were (180±46)and(185±5)ng/g at 30 and 60 d after injection of MSCs respect ively, and the contents of NGF were(115±29)and(108±34)ng/g, which were sig nificantly higher than those of the model group.