中国卒中杂志2016，Vol.11Issue(5)：360-367,8.DOI:10.3969/j.issn.1673-5765.2016.05.006
缺氧预处理后骨髓源神经干细胞联合脑源性神经生长因子移植治疗大鼠脑缺血再灌注损伤的研究
Research of the Treatment on Neural Stem Cells of Bone Marrow by Hypoxia Preconditioning Joint with BDNF on Cerebral Infarction in Rats
摘要
Abstract
Objective To investigate the curative effect of joint treatment on source neural stem cells of bone marrow (BMSCs-NSCs) by hypoxic preconditioned and brain derived neurotrophic factor (BDNF) stereotactic transplantation on cerebral infarction in rats, so as to provide animal experimental bases on the therapy of cell transplantation on brain infarction in plateau areas. Methods A total of 72 SD rats were randomly divided into hypoxia precondition group (n=36) and normal oxygen group (n=36). Acute hypoxic preconditioning (HPC) was performed for 3 days before molding in hypoxia precondition group. Two groups of rats were made the model of <br> middle cerebral artery occlusion reperfusion (MCAO/R). Each group was divided into 3 subgroups: BMSCs-NSCs+BDNF group (n=12), BMSCs-NSCs group (n=12) and control group (n=12), and each subgroup was respectively transplanted with stereotactic MSCs-NSCs combined with BDNF, MSCs-NSCs, and DMEM/F12 culture medium to the ipsilateral caudate nucleus of rats brain infarction. After transplantation, neurological function scoring was performed at 3 d, 7 d, 14 d, 21 d, 28 d and 35 d. Tworats were sacriifce from each group after been scored. The migration path of positive cells of 5-Bromo-deoxyUridine (Brdu) of the tissue of brain by immunohistochemistry staining. The expressions of CD133, Nestin, MAP-2, beta-tubullin, GFAP, GalC were detected by immunolfuorescence staining to understand the neural differentiation in bone marrow-derived, and to observe its curative effect. Results At 7 d, 14 d, 21 d, 28 d and 35 d, neurological function scoring were signiifcantly lower than 3 d in BMSCs-NSCs+BDNF and BMSCs-NSCs group of hypoxia precondition group and normal oxygen group. At 3 d after transplantation, in subgroup of control, neurological function scoring in hypoxia precondition group were signiifcantly lower than normal oxygen group (P=0.040). At 7 d after transplantation, in subgroup of BMSCs-NSCs+BDNF, neurological function scoring in hypoxia precondition group were signiifcantly lower than normal oxygen group (P=0.031). Whether in hypoxia precondition group or normal oxygen group, each index of integral optical density (IOD) in BMSCs-NSCs+BDNF group was higher than BMSCs-NSCs group (P<0.001), and each index of IOD in BMSCs-NSCs+BDNF group and BMSCs-NSCs group was higher than the control group (P<0.001). Conclusion The curative effect was obvious improvement by the joint treatment on BMSCs-NSCs by hypoxic preconditioned and BDNF stereotactic transplantation. Hypoxia preconditioning does not promote the differentiation of exogenous MSCs-NSCs, but can signiifcantly improve the neurological function of rats. Hypoxic preconditioning treatment may promote the proliferation and differentiation of endogenous MSCs.关键词
缺氧预处理/骨髓源神经干细胞/脑源性神经生长因子/立体定向移植Key words
Hypoxia precondition/Source neural stem cells of bone marrow/BDNF/Stereotactic transplantation引用本文复制引用
雷延成,吴世政,张淑坤,侯倩,才鼎,肖宗宇,陈晓娟..缺氧预处理后骨髓源神经干细胞联合脑源性神经生长因子移植治疗大鼠脑缺血再灌注损伤的研究[J].中国卒中杂志,2016,11(5):360-367,8.基金项目
青海省科技计划项目 （）
