Objective To explore the effects of erythropoietin （EPO） on the proliferation and differentia- tion of neural stem cells and on the cognition function of vascular dementia （VD） rats. Methods Totally 45 Sprague-Dawlev （SD） rats were randomly and equally divided into the sham control group, the VD group, and the treatment group. The VD rat model was established by performing cerebral ischemia/reperfusion repeatedly and given an intraperitoneal injection sodium nitroprusside. The rats from the treatment group received an intro- peritoneal injection of EPO after the establish of VD model, and the animals from the others were treated with normal saline. The learning-memory abilities were measured by using computerized shuttle-training case and the proliferation and differentiation of neural stem cells were detected by immunofluorescence staining. Results The active avoidance reaction （AAR） ratio in the VD group was significantly decreased compared with the sham control group （P 〈0.01 ）, but that in the treatment group was higher than the VD group （P 〈0. 01 ） though still lower than the sham group （P 〈 0.01 ）. During the 4 weeks we observed, BrdU labeled cells were migrated from the subgranular zone to granule cell layer. In 1 week after the model established, the number of BrdU labeled cells in the VD group was significantly larger than in the sham control group, but lower than that in the treatment group （P 〈 0. 01 ）. Immunofluorescence staining showed that the number of BrdU and DCX double la- beled cells in the treatment group was significantly larger than that in the VD group. In 4 weeks, the number of BrdU labeled cell was decreased in each group, especially in the VD group, and the number of BrdU and NSE double labeled cells in the treatment group was significantly larger than that in the VD group. But the per- centage of BrdU-labeled cells co-labeled with DCX/NSE had no significant difference. Conclusion EPO treatment enhances the proliferation of neural stem cells and improves the ability of learning and memory in VD rats, but has no obvious influence on the differentiation of the neural stem cells.

目的探讨促红细胞生成素(erythropoietin,EPO)对血管性痴呆(vascular dementia,VD)大鼠神经干细胞(neural stem cell,NSC)增殖、分化及认知功能的影响。方法SD大鼠45只,按随机数字表法分为对照组、VD组和治疗组;改良2-VO+硝普钠法建立VD大鼠模型;治疗组腹腔注射EPO;采用穿梭箱系统检测大鼠认知功能;免疫组化法检测神经干细胞增殖分化情况。结果行为学测试:VD组大鼠AAR比率显著低于对照组(P<0.01);治疗组大鼠AAR比率显著高于VD组(P<0.01),但仍显著低于对照组(P<0.01)。免疫组化结果:BrdU(5-Bromodeoxyuridine)标记阳性细胞随时间推移从海马颗粒下层(the subgranular zone,SGZ)向颗粒细胞层(granule cell layer,GCL)迁移。造模后1周,VD组BrdU标记阳性细胞数明显高于对照组(P<0.01),低于治疗组(P<0.01);治疗组大鼠BrdU+DCX(doublecortin)双标阳性细胞数明显高于VD组(P<0.01)。造模后4周,各组BrdU标记阳性细胞数与造模后1周相比均有明显下降,其中VD组下降最明显。治疗组BrdU+NSE(neuron-specific-enolase)双标阳性细胞数明显多于VD组(P<0.01)。各组大鼠各时相点BrdU标记阳性细胞数中神经元所占比例无统计学差异(P>0.05)。结论腹腔注射EPO可促进VD大鼠脑内NSC增殖,显著改善大鼠认知功能,但对NSC分化无明显影响。

重庆市 自然科学基金(2008AC5119)；重庆市医学会神 经病学专委会 “步长杯”基金重点项 目(2008) Supported hy the Natural Science Foundation ofChongqing(2008AC5119)and the Key Prc~ m of“Buchang Cup”Foundation of Chongqing Neurology Medical Association(2008)