摘要
目的：研究小鼠诱导性多能干细胞（iPSCs）移植对宫内缺氧新生鼠脑损伤的治疗作用及机制。方法：于孕14d开始孕鼠置于动物缺氧培养箱中，制作胎鼠宫内缺氧模型。孕鼠分娩后新生鼠经侧脑室注入BrdU标记的iPSCs悬液移植组和PBS缺氧组，对照组不治疗，H—E染色观察脑组织形态学变化、八臂迷宫测试动物记忆功能、免疫组织化学检测脑BrdU阳性细胞和神经颗粒素（Ng）和神经元烯醇化酶（NSE）的表达、原位杂交检测血管内皮生长因子mRNA（VEGFmRNA）的表达。结果：移植组小鼠的学习记忆能力和脑皮质区细胞结构较缺氧组均明显改善；脑切片检出BrdU阳性细胞存在，缺氧组Ng和NSE阳性细胞表达较对照组显著减少，而VEGFmRNA的表达较对照组显著增加；移植组Ng、NSE和VEGFmRNA表达均较缺氧组显著增加。结论：小鼠iPSCs移植于宫内缺氧的新生小鼠脑中，可减轻缺氧神经元的损伤和提高学习能力，其机制可能通过上调VEGFmRNA和Ng的表达有关。
Objective： To investigate the effect and mechanism of mouse induced pluripotent stem cells （iPSCs） transplantation for neonatal mouse with intrauterin hypoxia. Methods： Female mice were divided randomly into three groups： comrol group （CG）, hypoxia group （HG） and transplantation group （TG）. On the 14th day of mouse pregnancy, HG and TG were put into the incubator to make the model of intrauterine anoxic. The iPSCs marked with BrdU and PBS were respectively injected into the cerebral ventricle of transplantation group and model group and the control group was not treated. BrdU-positive cells and the expression of neurogramin（Ng） and neuron-specific enolase（NSE） proteins were detected by immunohistochemistry following transplantation. Vascular endothelial growth factor mRNA（VEGF mRNA） was detected by in situ hybridization. The learning and memory functions were tested with eight-arm maze. Results： Compared with the hypoxia group, the function of learning and memory was significantly improved in the transplantation group. BrdU positive cells were detected in the transplantation group. IOD of Ng and NSE positive cells in HG was less obvious than that in CG; But IOD of VEGF mRNA positive cells was higher than that in CG; IOD of Ng, NSE and VEGF mRNA positive cells in TG were significantly higher than that in HG. Conclusion ： iPSCs transplanted into the cerebral ventricles can reduce the hypoxic injury to neurons, and promote axonal growth and extension, which may upregulate the expression of VEGF mRNA to ameliorate the microenvironment.
出处
《解剖学杂志》
CAS
CSCD
北大核心
2016年第1期26-29,F0002,共5页
Chinese Journal of Anatomy
基金
河南省科技厅自然科学基金(132300410170)
河南省教育厅项目(12B320011)
漯河医学高等专科学校项目(2013-S-LMC27)
关键词
诱导性多能干细胞
移植
宫内缺氧
脑损伤
induced pluripotent stem cells
transplantation
intrauterin hypoxia
brain damage
作者简介
E-mail：lichenyue3@aliyun．com
通讯作者，E-mail：573373763@qq．com
