左心室移植人脐血单个核细胞治疗大鼠脑出血的microPET-CT评价及机制

Left ventricular transplantation of human umbilical cord blood mononuclear cells in the treatment of cerebral hemorrhage in rats: micro PET-CT evaluation and therapeutic mechanism

背景:近年来,出现了针对脑出血的新型干细胞移植疗法,但对于人脐血单个核细胞的研究还比较少,以micro PET-CT评价其效果的研究更为稀少。目的:通过Longa评分、micro PET-CT评价人脐血单个核细胞经左心室途径移植治疗大鼠脑出血模型的效果并探讨其部分治疗机制。方法:以二次注血/退针法制作大鼠脑出血模型,实验组大鼠脑出血造模成功后经左心室移植人脐血单个核细胞,对照组大鼠脑出血后自然转归,分别于移植前及移植后3,7,14,21 d对两组大鼠进行Longa5级评分、micro PET-CT图像分析,ELISA法测定脑匀浆中血管紧张素1水平。结果与结论:(1)实验组及对照组组内各时间点Longa5级评分均随时间变化逐渐降低(P<0.05)。实验组较对照组Longa5级评分降低更明显(P<0.05);(2)移植后第7,14,21天,实验组及对照组血肿中心、血肿周围代谢(SUV%)水平均逐渐升高(P<0.05)。实验组较对照组血肿中心、血肿周围代谢更高(P<0.05);(3)移植后第7,14,21天,实验组及对照组血肿及周围体积逐渐减小(P<0.05)。实验组较对照组血肿及周围体积更小(P<0.05);(4)对照组组内各时间点血管紧张素1水平随时间变化逐渐升高(P<0.05),实验组组内各时间点血管紧张素1水平逐渐升高至移植后14 d达峰值,移植后21 d又下降(P<0.05)。实验组较对照组血管紧张素1水平更高(P<0.05);(5)结果表明,经左心室途径移植人脐血单个核细胞能够改善脑出血大鼠的神经功能,促进脑内血肿体积减小及血肿区代谢恢复,增高脑内血管紧张素1表达水平,这提示人脐血单个核细胞移植可能通过调节血管生成过程而促进脑出血损伤区的修复。

BACKGROUND:In recent years,new stem cell transplantation therapies for cerebral hemorrhage have emerged,but little is reported on human umbilical cord blood mononuclear cells(HUCB-MNCs),especially on micro PET-CT evaluation of HUCB-MNCs effects.OBJECTIVE:To evaluate the therapeutic effect of HUCB-MNCs in a rat model of cerebral hemorrhage by Longa and micro PET-CT and to explore the therapeutic mechanism.METHODS:Models of cerebral hemorrhage were established in rats using secondary blood injection/needle retraction method.The rats in the experimental group were treated with HUCB-MNCs via left ventricular transplantation,and those in the control group received no treatment.Before and after transplantation(3,7,14,21 days),the rats in the two groups were evaluated using Longa 5 scores and micro PET-CT images.ELISA was used to detect the level of angiotensin 1 in the brain homogenate.RESULTS AND CONCLUSION:Longa 5 scores in the two groups were gradually decreased with time(P<0.05).Compared with the control group,the Longa 5 scores in the experimental group decreased more significantly(P<0.05).The standard absorption value(SUV%)in the center of hematoma and perihematomal region increased gradually in the two groups at 7,14,21 days after transplantation,but it was significantly higher in the experimental group than the control group(P<0.05).The volume of hematoma and surrounding tissues was gradually reduced in the two groups,especially in the experimental group,at 7,14,21 days after transplantation(P<0.05).The level of angiotensin 1 in the control group increased gradually with time(P<0.05),while the level of angiotensin 1 in the experimental group gradually increased,peaked at 14 days and then reduced at 21 days after transplantation(P<0.05).The level of angiotensin 1 was higher in the experimental group than the control group(P<0.05).Overall,these findings reveal that HUCB-MNCs via left ventricular transplantation can improve neurologic function of rats,reduce hematoma,recover hematoma metabolism,and increase the level of angiotensin 1 in the rat brain,indicating that HUCB-MNCs transplantation can promote the repair of cerebral hemorrhage through neo-angiogenesis regulation.