甘露醇促进人脐血CD34+细胞通过血脑屏障静脉迁移至高血压脑梗死大鼠脑组织 |
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作者姓名: | 余国龙 欧雅莉 杨天伦 方 立 胡 柯 |
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作者单位: | 中南大学湘雅医院心内科,湖南长沙市 410008 |
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基金项目: | 国家自然科学基金资助项目(30572079)。 |
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摘 要: | 背景:单纯脐血细胞经静脉移植治疗脑梗死疗效有限,移植细胞经血脑屏障迁入脑内数量不足为重要原因之一。
目的:观察血脑屏障开放剂甘露醇对人脐血CD34+细胞经静脉移植治疗高血压大鼠脑梗死疗效的影响。
方法:分离人脐血CD34+细胞,脂质体方法转染pEGFPF质粒,制备pEGFP-CD34+细胞;45只雄性SD大鼠经线栓法建立大脑中动脉栓塞模型,造模后24 h随机分为3组:实验组注射1×106 GFP-CD34+细胞,继之注射20%甘露醇2 g/kg;阳性对照组注射1×106 GFP-CD34+细胞;空白对照组注射等量生理盐水。
结果与结论:①荧光显微镜下实验组每张切片脑组织GFP标记阳性的绿色荧光细胞计数平均值显著多于阳性对照组。②移植后第7天治疗组与其他各组神经功能损害评分差异无显著性意义;移植后28 d,各组神经功能均有不同程度恢复,实验组神经功能恢复明显优于阳性对照组和空白对照组(P < 0.05)。③实验组与其他两组相比,大鼠脑梗死体积均显著减少。④实验组脑组织匀浆胶质细胞源性神经营养因子水平较阳性对照组、空白对照组明显增高。提示血脑屏障开放剂甘露醇促进静脉移植CD34+细胞通过血脑屏障迁入至脑组织,并增强静脉移植CD34+细胞治疗脑梗死的疗效。
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关 键 词: | 血脑屏障开放剂 CD34+细胞 细胞移植 静脉途径 脑梗死 |
收稿时间: | 2011-01-11 |
Mannitol improves the efficacy of intravenous transplantation of human umbilical cord blood CD34+ cells for cerebral infarction in hypertensive rats |
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Authors: | Yu Guo-long Ou Ya-li Yang Tian-lun Fang Li Hu Ke |
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Institution: | Department of Cardiology, Xiangya Hospital of Central South University, Changsha 410008, Hunan Province, China |
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Abstract: | BACKGROUND: Intravenous transplantation of human umbilical cord blood cells (HUCBCs) in treatment of cerebral infarction is limited. Only a small fraction of the grafted cells appears to survive at the damaged brain and the behavioral recovery is only partial.
OBJECTIVE:To evaluate the ability of Mannitol, a blood brain barrier (BBB) permeabilizer, to enhance neuroprotective effects of intravenously administered HUCBCs for cerebral infarction in spontaneous hypertensive rats.
METHODS:CD34+ cells isolated from HUCB were transfected by GFP plasmid with liposome method. Forty-five adult male spontaneous hypertensive rats with middle cerebral artery occlusion were randomly divided into three groups at 24 hours after modeling, each of 15: Experimental group, GFP-CD34+ cells (1×106) and 20% Mannitol (2 g/kg) were administrated intravenously at 24 hours after modeling; Positive control group, GFP-CD34+ cells (1×106) were only injected intravenously at same time; Blank control group, normal saline was injected at same time.
RESULTS AND CONCLUSION:①The number of GFP positive cells in cerebral tissues in the experimental group was increased significantly compared to the positive control group. ②No significant difference was found in the neurologic function scores at day 7 after transplantation among the three groups; but at day 28 after transplantation, the neurologic function in the experimental group was improved significantly compared with the positive or blank control group (P < 0.05). ③The cerebral infarct volume in the experimental group was significantly decreased compared with the positive or blank control group. ④The glial cell line-derived neurotrophic factor level in cerebral tissue in the experimental group was significantly increased compared with the positive and blank control groups. The results suggested that Mannitol enhanced CD34+ cells to migrate into ischemic-injured cerebral tissues, and to improve the efficacy of CD34+ cells delivered intravenously for cerebral infarction in spontaneous hypertensive rats. |
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