人脐血干细胞海马CA1区移植及GM1腹腔注射治疗大鼠血管性痴呆  

Combination of human cord blood stem cells transplantion into hippocampus CA1 area and intraperitoneal injection of monosialoganglioside treats vascular dementia rats

作　　者：李莹[1] 王景周[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所神经内科,重庆400042

出　　处：《第三军医大学学报》2008年第12期1154-1158,共5页Journal of Third Military Medical University

基　　金：重庆市科委攻关项目(7830)~~

摘　　要：目的探讨人脐血干细胞(human cord blood stem cells,HCBSCs)海马移植对血管性痴呆(vascular dementia,VD)模型大鼠的治疗作用,并观察单唾液酸神经节苷脂(monosialoganglioside,GM1)是否具有协同作用。方法人脐血干细胞经培养和纯化,以BrdU标记;大鼠行双侧颈动脉(2VO)结扎制作血管性痴呆模型;按随机数字表法分为对照组、模型组、细胞移植组、GM1注射组、细胞移植联合GM1注射组(简称联合治疗组);Morris水迷宫系统检测大鼠行为学;立体定向仪将标记细胞立体定向注射到大鼠海马CA1区;比较术后24 h、3、7、14、21、28 d各时相点大鼠行为学变化;免疫组织化学染色观察BrdU标记细胞存活情况,大鼠脑内生长相关蛋白(growth associated protein-43,GAP-43)阳性细胞增殖情况。结果2VO模型大鼠术后28 d学习记忆能力下降;经治疗各组均有所恢复,治疗组与模型组相比有显著差异,联合治疗组差异最明显。BrdU标记细胞注射到大鼠脑中可存活,并在海马及血管周围区聚集,联合治疗组14 d后比细胞移植组存活多;注射周围区及皮层GAP-43阳性细胞增殖,GM1注射组也可促进GAP-43阳性细胞增殖,联合治疗组阳性细胞数量最多。结论脐血干细胞立体定向注射至大鼠海马CA1区可存活,并可刺激GAP-43阳性细胞增殖,GM1治疗有协同作用。Objective To observe the effect of the human cord blood mesenchymal stem cells transplanted into hippocampus CA1 area of vascular dementia rats, and the possible synergistic effect of intraperitoneal injection of monosialoganglioside （GM1）. Methods Human cord blood was collected with informed consent, and the stem cells were screened, cultured, purified, then were marked with BrdU. A total of 120 2VO dementiaestablished rats were randomly and equally divided into the model group, cell transplant group （1.5 ×10^5 cultured cells）, GM1 injection group（ 10 mg/kg, once a day for 14 d）, and combination group, and another 5 normal rats served as control group. Five rats of every group besides control group were killed on days 1,3, 7, 14, 21 and 28 for pathological observation. The function of learning and memory were examined with the Morris water maze on day 28. The survival BrdU marked cells and the growth associated protein-43 （ GAP-43 ） positive cells were detected by immunohistochemical staining. Results The learning and memory ability was decreased obviously in the rats of model group, but the situation was improved in the 3 treatment group, especially in combination group. The transplanted cells were survival in the brain and gathered in the hippocampus area, and those in combination group demonstrated more survival cells from day 14. There were more proliferated-GAP- 43-positive cells around the injection site and in the cortex in the treatment groups, and the most cells were observed in combination group. Conclusion The human cord blood stem cells can survive in rat brain, and improve the cognitive function of vascular dementia rats. Intraperitoneal injection of GM1 exerts a synergistic effect in this treatment.

关 键 词：人脐血干细胞 血管性痴呆 单唾液酸神经节苷酯 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学] R741.05[医药卫生—基础医学]