丹参酮Ⅱ联合骨髓间充质干细胞移植促进脑梗死后的神经再生

摘要

BACKGROUND:Studies have shown that tanshinone II can improve microcirculation, dilate cerebral blood vessels, increase cerebral blood flow, reduce infarct size, and improve brain function after cerebral metabolic disorder. OBJECTIVE:To investigate the effect of tanshinone II combined with bone marrow mesenchymal stem cel transplantation on nerve regeneration folowing cerebral infarction in rats. METHODS:Rat models of acute cerebral infarction were prepared using the thread occlusion method and then given tanshinone II combined with bone marrow mesenchymal stem cel transplantation (combined group), bone marrow mesenchymal stem cel transplantation (cel transplantation group), and no treatment (model group), respectively. Neuromotor function was assessed using Longa scores. Expression of brain-derived neurotrophic factor gene around the infarction region was detected using RT-PCR. Cel apoptosis was detected using TUNEL. Immunohistochemistry staining was used to determine peri-cortex Nogo-A and NgR protein expression at the infarction region. RESULTS AND CONCLUSION:Longa scores, apoptotic index, and expression of Nogo-A and NgR proteins exhibited significant differences among three groups (P< 0.05) as folows: combined group < cel transplantation group < model group. Conversely, the expression of brain-derived neurotrophic factor gene was highest in the combined group successively folowed by the cel transplantation group and model group (P< 0.05). These data show that tanshinone II combined with bone marrow mesenchymal stem cel transplantation accelerate the recovery of neurologic function and promote nerve regeneration after cerebral infarction by incresing mRNA expression of brain-derived neurotrophic factor.%背景：有研究表明，丹参酮Ⅱ能改善微循环，扩张脑血管，增加脑血流量，降低脑梗死面积，改善脑梗死后造成的脑功能代谢障碍。　　目的：观察丹参酮Ⅱ联合骨髓间充质干细胞移植对大鼠脑梗死后受损神经再生的影响。　　方法：采用线栓法制作急性脑梗死大鼠模型，进行丹参酮Ⅱ联合骨髓间充质干细胞移植，并设骨髓间充质干细胞移植组和模型组进行对比。采用Longa评分进行神经运动功能的评定；采用RT-PCR法检测大鼠脑梗死区周围脑源性神经营养因子基因的表达；采用TUNEL法检测大脑梗死区细胞凋亡情况；利用免疫组织化学检测梗死灶周围皮质Nogo-A和NgR蛋白的表达。　　结果与结论：①Longa 评分、凋亡指数、Nogo-A 和 NgR 蛋白表达：联合组<骨髓间充质干细胞移植组<模型组(P<0.05)；②脑源性神经营养因子基因表达：联合组>骨髓间充质干细胞移植组>模型组(P<0.05)；③结果证实，丹参酮Ⅱ联合骨髓间充质干细胞移植可通过抑制梗死区Nogo-A和NgR蛋白的表达，促进脑源性神经营养因子基因的表达，促进神经功能恢复，促进脑梗死后神经再生。