摘要
目的:观察体外培养大鼠骨髓基质细胞(MSCs)立体定向移植入全脑照射损伤模型大鼠海马内是否对其认知功能有修复作用。方法:取2～3周龄SD大鼠6只用于MSCs体外分离、培养和增殖。取成年雄性SD大鼠48只,数字随机分为假照射组、单纯照射组、照射+PBS组和照射+MSCs组,各12只,采用10Gy单次全脑照射模型,假照射组以铅档块屏蔽,照射+MSCs组为制模后1周MSCs用Brdu标记后在立体定向仪下移植入全脑照射模型大鼠海马内,假照射组和照射+PBS组大鼠用同样方法将等量PBS注入。4周后通过Y迷宫法观察大鼠认知功能变化,免疫组织化学法检测海马血管内皮生长因子(VEGF)蛋白表达变化,免疫荧光双染色观察BrdU标记细胞及分化的功能细胞。结果:与假照射组比较,单纯照射组大鼠的学习记忆能力明显受损,F=24.86,P<0.01;海马VEGF蛋白表达明显增高,F=29.19,P<0.01。与单纯照射组比较,照射+MSCs组大鼠认知功能明显改善,F=14.86,P<0.05;海马VEGF表达明显降低,F=23.86,P<0.01。移植点附近见BrdU标记的MSCs存活,部分BrdU阳性细胞表达O4。结论:MSCs移植通过抑制VEGF表达可显著改善放射性脑损伤模型大鼠认知功能;MSCs移植入全脑照射大鼠海马内可存活,部分定向分化为少突胶质谱系细胞,但分化延迟。
OBJECTIVE：To explore whether the cultured mesenchymal stem cells （MSCs） derived from bone mar row in rats had the protect effect on the cognitive impairment after transplanted into the hippoeampus of whole-brain irra- diated rats. METHODS： MSCs from bone marrow of 2-3 weeks old（SD） rats were isolated and cultured aseptically. To- tally 48 adult SD rats were randomly and equally divided into four groups：sham-irradiation group, irradiation group,irradi- ation＋ MSCs group and irradiation＋PBS group, 12 rates in each group. The model of whole brain irradiation was estab- lished with the exposure of the brain of the rats to 4 Mev x-ray with a single-dose 10 Gy. The rats in sham-irradiation group were shielded with lead bricks. Irradiation＋ MSCs group was modeled seven days after irradiation, MSCs labeled with BrdU were transplanted into whole brain irradiated hippocampus with the aid of a stereotaxic instrument,irradiation group and irradiation＋PBS group were transplanted PBS by the same process. Four weeks later, the learning and memori- zing ability was measured with the Y maze test. The expression of vascular endothelial growth factor （VEGF） in hippo- campus was determined by immunohistoehemistry staining. Immuno-fluorescence staining was used to identify MSCs or cells derived from MSCs in the brain. RESULTS： Compared with the sham-irradiation groups, the learning and memori- zing abilities of irradiation groups were significantly affected （F= 24.86, P^0.01） and the expression of VEGF in rats were increased significantly （F= 29.19, P〈0.01）. Compared with irradiation group, the cognitive function of group trea- ted with MSCs was improved significantly （F= 14.86, P〈0.05）, and the expression of VEGF was decreased significantly（F= 23.86,P〈0.01）. Surviving MSCs labeled with BrdU were observed around the transplant point, and part of BrdU positive ceils were observed expression of 04. CONCLUSIONS： MSCs transplantation can improve the cognitive impair- ment of rats after whole brain irradiation through reducing the expression of VEGF. The MSCs which are transplanted in- to the hippocampus of whole-brain irradiated rats may survive and some MSCs could differentiate into oligodendrocyte lin- eage cells, but will defer the differentiation.
出处
《中华肿瘤防治杂志》
CAS
北大核心
2013年第11期815-819,共5页
Chinese Journal of Cancer Prevention and Treatment
基金
江苏省卫生厅重大科研(K200406)
关键词
骨髓基质细胞
电离辐射
细胞移植
少突胶质细胞
血管内皮生长因子
海马
mesenchymal stem cell
Ionizing radiation
cell transplantation
oligodendrocyte
vascular endothelialgrowth factor
hippocampus
