移植胶质细胞源性神经营养因子基因修饰骨髓基质干细胞对脑出血大鼠的神经保护作用

Neuroprotective effect of glial cell line-derived neurotrophic factor gene-modified bone marrow stromal cells transplantation on intracerebral hemorrhage in rats

背景:研究显示,细胞移植对脑出血脑损伤有保护作用,有学者在脑梗死后移植骨髓基质干细胞能促进大鼠神经功能恢复。目的:观察移植胶质细胞源性神经营养因子基因修饰的骨髓基质干细胞是否比单纯骨髓基质干细胞移植对脑出血有更好的保护作用。方法:采用自体血制作大鼠脑出血模型,36只SD成年大鼠随机抽签法分为3组,每组按不同时间点分为2个亚组,每个时间点6只。胶质细胞源性神经营养因子/骨髓基质干细胞组、骨髓基质干细胞组分别在脑出血壳核注射胶质细胞源性神经营养因子基因修饰的骨髓基质干细胞、骨髓基质干细胞20μL/只;对照组注射生理盐水20μL。分别在1,2周处死大鼠,免疫组织化学染色观察突触素和神经生长相关蛋白在脑出血周边区的表达。结果与结论:各时间点胶质细胞源性神经营养因子/骨髓基质干细胞组的突触素和神经生长相关蛋白43免疫阳性产物比骨髓基质干细胞组和对照组显著增加(P<0.05)。提示胶质细胞源性神经营养因子基因修饰的骨髓基质干细胞比单一骨髓基质干细胞对大鼠脑出血有更好的保护作用。

BACKGROUND：Previous studies have demonstrated that cell transplantation has neuroprotective effect on intracerebral hemorrhage,and some researches have indicated that transplantation of bone marrow stromal cells（BMSCs） can promote neural function recovery after cerebral infarction.OBJECTIVE：To explore whether transplantation of BMSCs-modified by glial cell line-derived neurotrophic factor gene（GDNF） gene provides a better therapeutic effect than native BMSCs after stroke.METHODS：Totally 36 SD rats were induced intracerebral hemorrhage models by injecting autologous arterial blood,and then divided into 3 groups（n = 6）,each group was assigned into 2 sub-groups.Rabbits in each group were stereotaxically grafted with 20 μL GDNF/BMSCs,BMSCs or saline respectively.The rats were executed at 1 and 2 weeks after operation,and immunohistochemistry was used to observe the expressions of synaptophysin（Syn） and growth associated protein-43（GAP-43） in the margin of the hemorrhagic focus.RESULTS AND CONCLUSION：Compared with the BMSCs and control groups,both Syn-immunoreactive and GAP-43-immunoreactive products were significantly increased in the GDNF/BMSCs group（P〈 0.05）.Present results demonstrate that transplantation of GDNF gene-modified BMSCs provides better neuroprotection than native BMSCs delivery for stroke.