Department of Neurology, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Chin Med J (Engl). 2010 Dec;123(24):3620-5.
Aging is an important risk factor for vascular dementia, and D-galactose (D-gal) injection can simulate the pathology of aging. Two-vessel occlusion of common carotid arteries (2VO) is the most popular model for vascular dementia. This study was aimed to investigate the possibility of D-gal injection plus 2VO simulating cognitive impairment of aging vascular dementia; and whether transplanted bone marrow stromal cells (BMSCs) can improve the cognitive function induced by D-gal injection plus 2VO.
Totally 30 male Sprague-Dawley rats were divided into 5 groups equivalently: control group, D-gal group, D-gal + 2VO group, D-gal + 2VO + saline water group, and D-gal + 2VO + BMSCs group. Aging hypoperfusion rats were created by subcutaneous injection of D-gal and occlusion of two common carotid arteries. BMSCs or saline water was stereotactically transplanted into the subventricular zone as treatment vehicles at 24 hours post operation. Two-way repeat analysis of variance (ANOVA) was used for significance analysis of 5 groups at 6 weeks post transplantation; moreover, Tamhane's test (equal variance not assumed) and least significant difference (LSD) test (equal variance assumed) were used for pairwise comparison in Morris water maze (MWM).
Transplanted BMSCs distributed around the lateral ventricles and acquired the phenotypes of neurons and astrocytes. In terms of swimming path distance and escape latency in MWM, D-gal + 2VO + BMSC group showed significant improvement than the D-gal + 2VO group but was still obviously worse than the control group (both P < 0.05). There was no significant difference in swimming speed for all 5 groups.
D-gal plus 2VO induces cognitive dysfunction. The engrafted BMSCs exhibit the beneficial effect on cognitive function via promotion interactively with host brain.
衰老 是血管性痴呆的一个重要危险因素,D-半乳糖(D-gal)注射可模拟衰老的病理学。双侧颈总动脉结扎(2VO)是血管性痴呆最常用的模型。本研究旨在探讨 D-半乳糖注射加 2VO 模拟衰老血管性痴呆认知障碍的可能性;以及移植骨髓基质细胞(BMSCs)是否能改善 D-半乳糖注射加 2VO 引起的认知功能障碍。
将 30 只雄性 Sprague-Dawley 大鼠随机等分为 5 组:对照组、D-gal 组、D-gal+2VO 组、D-gal+2VO+生理盐水组和 D-gal+2VO+BMSCs 组。通过 D-gal 皮下注射和双侧颈总动脉结扎,建立衰老低灌注大鼠模型。术后 24 小时,立体定向将 BMSCs 或生理盐水移植到侧脑室下区作为治疗载体。6 周后,采用双向重复方差分析(ANOVA)对 5 组进行显著性分析;此外,采用 Tamhane 检验(方差不齐时假设)和最小显著差(LSD)检验(方差齐时假设)进行 Morris 水迷宫(MWM)中的两两比较。
移植的 BMSCs 分布在侧脑室周围,获得神经元和星形胶质细胞的表型。在 MWM 的游泳路径距离和逃避潜伏期方面,D-gal+2VO+BMSC 组比 D-gal+2VO 组有明显改善,但仍明显差于对照组(均 P<0.05)。5 组的游泳速度无明显差异。
D-gal 加 2VO 可诱导认知功能障碍。移植的 BMSCs 通过与宿主大脑的相互作用,对认知功能产生有益的影响。