骨髓间充质干细胞颈内动脉移植在血管性痴呆大鼠脑内存活迁移及对胆碱能系统的影响

目的观察颈内动脉移植骨髓间充质干细胞(MSC)透过血脑屏障在血管性痴呆(VaD)大鼠脑内存活、迁移及对海马乙酰胆碱(Ach)含量、乙酰胆碱酯酶(AchE)活性和认知能力的影响。方法选72只Wistar大鼠分为对照组、模型组和治疗组,每组又分4、8周2个时相点,每时相点12只。制作VaD大鼠模型,治疗组于术后24h颈内动脉移植0.5ml骨髓MSC。移植4、8周后检测移植细胞在VaD大鼠脑内存活、迁移及学习记忆能力,并检测海马区Ach含量及AchE活性。结果颈内动脉移植后4周骨髓MSC在VaD大鼠脑实质中广泛分布,主要聚集至海马、大脑皮质等缺血易损伤区域。与对照组比较,模型组和治疗组术后4、8周大鼠学习记忆显著降低(P<0.01);与模型组比较,治疗组术后4、8周大鼠学习记忆显著改善(P<0.01),细胞移植后治疗组Ach含量和AchE活性显著升高,差异有统计学意义(P<0.01)。结论骨髓MSC颈内动脉移植后可透过血脑屏障明显改善VaD大鼠胆碱能系统的功能,调节脑内Ach生理代谢,促进缺血损伤后脑组织的修复与再生,增强学习记忆能力。

Survival and migration of bone marrow MSC in brain of VaD rats and their effect on cholinergic system

Objective To observe the effect of survived and migrated bone marrow MSC on Ach level and AchE activity in VaD rats.Methods Seventy-two Wistar rats were divided into control, model and treatment groups(24in each group).A VaD rat model was established.The survived and migrated bone marrow MSC and learning-memory ability,Ach level and AchE activity were assayed 4and 8weeks after 0.5ml of bone marrow MSC was transplanted into the carotid artery. Results The bone marrow MSC were widely distributed in the brain tissue of VaD rats,especially in hippocampus and cerebral cortex.The learning-memory ability was significantly lower in model group and treatment group than in control group(P<0.01)whereas the learning-memory ability,Ach level and AchE activity were significantly higher in treatment group than in model group(P<0.01).Conclusion Bone marrow MSC can migrate to the ischemia-injured areas,improve the cholinergic system function,regulate the Ach metabolism,repair the ischemia-injured brain tissues and strengthen the learning-memory ability of VaD rats.