摘要
目的观察骨髓间充质干细胞(MSCs)移植对大鼠缺血性脑损伤后神经功能恢复的作用并探讨其作用机制。方法体外培养MSCs;线栓法制作SD大鼠脑缺血2h再灌注模型,24h后将标记5-溴脱氧尿嘧啶(B rdu)的MSCs通过颈动脉移植入脑缺血大鼠体内;采用神经功能缺损评分检测大鼠神经系统功能;用苏木素-伊红(HE)染色以观察梗死灶的部位和范围;用免疫组化方法检测脑内MSCs的迁移及分泌营养因子的分泌情况;寡核苷酸末端脱氧核糖核酸介导的dUTP缺口末端标记法(TUNEL)原位检测缺血周边区皮质神经细胞凋亡的情况。结果动脉移植后,MSCs在脑内存活、迁移,同时分泌血管内皮细胞生长因子(VEGF)、脑源性神经营养因子(BDNF)等多种神经保护性因子;显著上调BDNF和VEGF的表达,延长其高表达时程;并减少了神经细胞的凋亡。与模型组和PBS组相比,MSCs移植组神经功能明显改善;脑组织病理变化明显减轻(P<0.05)。结论动脉移植MSCs治疗大鼠缺血性脑损伤具有较好的疗效。MSCs分泌多种神经保护性营养因子及减少缺血周边区神经细胞凋亡可能是其主要机制之一。
To investigave the effect and mechanism of bone marrow stromal cells （MSCs） transplanted for treatment of cerebral ischemia - reperfusion injury in rats. Methods MSCs were isolated from the bone marrow of SD rats , cultured in vitro. Rats cerebral ischemia 2 hourreperfusion injury model was established with suture emboli method. MSCs labeled with Bromodeoxyuridine（ Brdu ） were transfered into MSCs treated group rats through external carotid artery 24 hours later after 2 hours of middle cerebral attery occlusion . The neurological deficits of rats were evaluated at every day after operation. Part and area of infarct were investigated by HE dyeing. The distribution of MSCs and the expression of neurotrophic factors were investigated by immunohistochemistry . The apoptosis of the neural cells was examined by terminal deoxyuncleotidyhransferase - mediated dUTP biotin nick - end. Results The transplanted MSCs of rats brain could survive, migrate, produce kinds of neurotrophic factors,such as VEGF、BDNF, markedly upregulate expression of VEGF,BDNF, delay neurotrophic factors high expression time , and reduce apoptosis of nerve cells . Significant recorvery ofneurological function and pathologic change was found in rats treated with MSCs compared with control rats. Conclusion The therapy of MSCs transplanted into rat brain following cerebral is-chemia is effective. It was one of the main protection mechanisms of MSCs by enhancing neurotrophic factors expression that could reduce apoptosis of nerve cells.
出处
《医药论坛杂志》
2006年第17期1-4,共4页
Journal of Medical Forum
基金
河南省卫生厅医学科技创新人才项目(20034024)
河南省科技厅自然科学基金(211040500)
关键词
骨髓间充质干细胞
移植
脑缺血再灌注
神经营养因子
凋亡
Marrow stromal cells
Cerebral ischemia - reperfusion
Transplantation
Neurotrophic factors
Apoptosis
