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骨髓基质细胞静脉移植治疗大鼠短暂性局灶性脑缺血
引用本文:钟池,钟春玖,罗玉敏,汪洋,秦震,沈馨亚.骨髓基质细胞静脉移植治疗大鼠短暂性局灶性脑缺血[J].中华神经医学杂志,2004,3(2):89-92,98.
作者姓名:钟池  钟春玖  罗玉敏  汪洋  秦震  沈馨亚
作者单位:1. 山东省潍坊市人民医院神经内科,山东,潍坊,261041;复旦大学附属华山医院神经病学研究所,上海,200040
2. 复旦大学附属中山医院神经内科,上海,200032
3. 复旦大学附属华山医院神经病学研究所,上海,200040
4. 复旦大学上海医学院解剖与组织胚胎学系,上海,200032
摘    要:目的探讨骨髓基质细胞静脉移植治疗大鼠短暂性局灶性脑缺血的可行性及其机制。方法将大鼠骨髓基质细胞在体外纯化、扩增并经BrdU标记后,经尾静脉移植到局灶性脑缺血大鼠体内,通过神经缺损评分观察移植后大鼠神经行为学改善情况,通过组织学方法观察移植到脑内的骨髓基质细胞表达脑源性神经营养因子、缺血灶周围细胞凋亡及脑微血管密度的变化。结果骨髓基质细胞移植组大鼠的神经缺损评分显著低于对照组(P<0.05);移植到脑内的骨髓基质细胞主要选择性分布于缺血灶周围区域并表达BDNF;骨髓基质细胞移植组大鼠梗死灶周围的凋亡细胞明显少于对照组(P<0.01)、微血管密度显著高于对照组(P<0.001)。结论经静脉注射移植骨髓基质细胞能够明显促进局灶性脑缺血大鼠的神经行为功能恢复;抗凋亡及促微血管增生可能是骨髓基质细胞移植治疗局灶性脑缺血的机制之一。

关 键 词:骨髓基质细胞  局灶性脑缺血  脑源性神经营养因子  细胞移植  凋亡  微血管密度
文章编号:1671-8925(2004)02-0089-004
修稿时间:2003年9月15日

The therapeutic effect of the intravenous administration of bone marrow stromal cells for treating transient focal cerebral ischemia in rats
ZHONG Chi,ZHONG Chunjiu,LUO Yumin,WANG Yang,QIN Zhen,SHEN Xinya.The therapeutic effect of the intravenous administration of bone marrow stromal cells for treating transient focal cerebral ischemia in rats[J].Chinese Journal of Neuromedicine,2004,3(2):89-92,98.
Authors:ZHONG Chi  ZHONG Chunjiu  LUO Yumin  WANG Yang  QIN Zhen  SHEN Xinya
Institution:ZHONG Chi,ZHONG Chunjiu,LUO Yumin,WANG Yang,QIN Zhen,SHEN Xinya Department of Neurology,Weifang People's Hospital,Weifang 261041,China,Department of Neurology,Zhongshan Hospital,Fudan University,Shanghai 200032,China,Institute of Neurology,Huashan Hospital,Fudan University,Shanghai 200040,China, Department of Anatomy,Histology and Embryology,Shanghai Medical College,Fudan University,Shanghai 200032,China
Abstract:Objective To explore the feasibility and the mechanism of the intravenous administration of bone marrow stromal cells (BMSCs) for treating transient focal cerebral ischemia in rats. Methods After purified, proliferated, and marked with BrdU, the BMSCs were injected intravenously into rats 7 days after focal cerebral ischemia. Neurological Deficits Score (NDS) were evaluated before and following 1, 7, 14, 21and 28 days of middle cerebral artery occlusion (MCAO). Rats were euthanized at 28 days after MCAO. Brain sections were stained with hematoxylin and eosin (HE) for surveying the volume of infarction. Slides were stained by the terminal deoxynucleotidyl transferase -mediated dUTP-biotin nick-end labeling (TUNEL) method for apoptosis detection in situ. Double-staining immunohistochemistry of brain sections was used to identify cell-specific brain-derived neurotrophic factor (BDNF) expression in bromodeoxyuridine-reactive BMSCs. And microvascular density in ischemic boundary zone was also detected with immunochemical staining of factor. Results NDS in BMSCs-transplanted group at 21th day and 28th day of MCAO was significantly lower than that in control group (P<0.05). Double immunostaining showed that grafted BMSCs had migrated to the ischemic boundary zone, survived and expressed BDNF. The number of apoptotic cells and the apoptotic rate in the BMSCs transplantation group decreased compared with that of control group (P< 0.01). The microvascular density was higher in the ischemic boundary zone of BMSCs-transplanted group than that in the control group (P<0.001). Conclusion The intravenous administration of BMSCs can promote the recovery of neurological function of rats with focal cerebral ischemia. The therapeutic effect of BMSCs on rats with focal cerebral ischemia may be derived from the reduction of apoptosis and the angiogenesis in the ischemic boundary zone.
Keywords:bone marrow stromal cells  focal cerebral ischemia  brain-derived neurotrophic factor  cell transplantation  apoptosis  microvascular density
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