关键词: 骨髓基质干细胞, 胶质细胞源性神经营养因子, 脑出血, 细胞移植, 反转录-聚合酶链式反应, 免疫组织化学, 大鼠

Abstract: Objective To explore the effects of bone marrow stromal cells (BMSCs) transplantation modified by glial cell line-derived neurotrophic factor (GDNF) gene on neuronal apoptosis and the expression of apoptosis-related genes in rats with intracerebral hemorrhage. Methods Forty-eight rats were used to establish the model of intracerebral hemorrhage by injecting with collagenase and heparin into caudate nucleus through stereotaxic apparatus.The rats were randomly divided into BMSCs group, GDNF/BMSCs group and saline group, and were stereotaxically grafed with BMSCs, GDNF/BMSCs and saline respectively at the 3rd day after operation. Each group was subdivided into two subgroups according to different refeeding time (1 week, 2 weeks). Neurological function and area of brain injury were assessed by neurological deficits score and HE staining respectively. Expression of GDNF mRNA was observed by RT-PCR. The number of neuronal apoptosis and the expressions of Bax and Bcl-xl in the margin of the hemorrhagic focus were observed by TUNEL and immunohistochemistry. Results Significant recovery of neurological function and increase of GDNF mRNA expression were found in the GDNF/BMSCs group compared with BMSCs and saline group. Both rate of brain injury area and the number of neuronal apoptosis in the GDNF/BMSCs group were significantly less than other groups. As compared with the BMSCs and saline group, the number of Bcl-xl positive cells increased in the GDNF/BMSCs group, while the number of Bax positive cells decreased. Conclusion The transplantation BMSCs modified by GDNF gene provides better neuroprotection than native BMSCs. The underlying mechanisms may be due to partly inhibited apoptosis, and the expression of up-regulated Bcl-xl and down-regulated Bax protein.

Key words: Bone marrow stromal cell, Glial cell line-derived neurotrophic factor, Intracerebral hemorrhage, Cell transplantation, RT-PCR, Immunohistochemistry, Rat