BMSCS对放射性脑损伤所致大鼠认知障碍的影响及海马病理学的改变

Effect of bone marrow mesenchymal stem cells on cognitive dysfunction caused by radiation-induced brain injury in rats and pathological changes in the hippocampus

目的 探讨大鼠骨髓间充质干细胞(Bone marrow mesenchymal stem cells, BMSCS)对大鼠放射性脑损伤(Radiation-induced brain injury, RIBI)后引发认知功能障碍的修复改善作用。方法 采用全骨髓贴壁法分离,提取,培养大鼠骨髓间充质干细胞。根据实验要求,选用SD成年雄性大鼠30只,并将其随机分组成3组,对照组(Control组)、放射性脑损伤组(RIBI组)和放射脑损伤+BMSCS组(BMSCS组),每组各10只。采用6 MeV电子线单次照射建立放射性脑损伤模型。使用4只4周龄的SD大鼠,分离培养大鼠骨髓间充质干细胞。BMSCS组在接受放射后的24 h和第8 d接受分别接受BMSCS的尾静脉注射治疗,单次注射剂量为3×10^(6)个细胞。造模21 d后,采用水迷宫实验对大鼠的认知能力进行评估,观察各组大鼠的学习记忆能力的改变。取各组大鼠海马组织行苏木素-伊红(HE)染色,在光镜下观察大鼠海马组织神经元的形态学变化。结果 与Control组相比,RIBI组大鼠逃避潜伏期显著延长,穿越平台次数减少(P<0.05);与RIBI组相比,BMSCS组大鼠逃避潜伏期缩短,穿越目标象限次数明显增加(P<0.05);在HE染色后,RIBI组神经细胞核皱缩,胞质肿胀,排列紊乱,大多呈空泡样改变;BMSCS组神经细胞病理性变化大多得到改善,小部分神经细胞仍有空泡样改变出现。结论 大鼠骨髓间充质干细胞可以通过对大鼠海马神经元的治疗,改善大鼠放射性脑损伤引起的认知功能障碍。

Objective To investigate the the repair and improvement effects of bone marrow mesenchymal stem cells(BMCSs)on cognitive dysfunction caused by radiation-induced brain injury(RIBI)in rats.Methods BMSCS from rats were isolated and cultured in vitro by using the whole bone marrow adherence method.According to the experimental requirements,30 adult SD rats were selected and were randomly divided into 3 groups:control group,RIBI group and BMSCS group,with 10 rats in each group.The model of radiation-induced brain injury was established by single irradiation of 6MeV electron wire.Bone marrow mesenchymal stem cells were isolated from 4 SD rats that aged 4 weeks and the cells were cultured.The BMSCS group received a tail vein injection of BMSCS at 24 hours and 8 days after radiation,with a single injection dose of 3×10^(6) cells.After 21 days of modeling,the cognitive ability of rats was evaluated by Morris Water Maze,and the changes of learning and memory ability of rats in each group were observed.The hippocampal tissues of rats in each group were stained with hematoxylin-eosin(HE),and the morphological changes of hippocampal neurons were observed under light microscope.Results Compared with the control group,the escape latency of rats in the RIBI group was significantly prolonged,and the frequency of crossing the platform was decreased(P<0.05).Compared with the RIBI group,the escape latency of rats in the BMSCS group was shortened,and the number of crossing the target quadrant was significantly increased(P<0.05).After HE staining,the nuclei of neurons in RIBI group were wrinkled,the cytoplasm was swollen,the arrangement was disordered,and most of them showed vacuole-like changes.The pathological changes of nerve cells in BMSCS group were mostly improved,however,a small portion of nerve cells still showed vacuole-like changes.Conclusions BMSCS can improve cognitive dysfunction caused by radiation brain injury in rats by treating hippocampal neurons.