不同途径移植人脐血单核细胞对脑出血大鼠神经功能的影响

Effect on Different Pathways of Transplantation of Human Umbilical Cord Blood Stem Cells on Neural Function in Rats with Cerebral Hemorrhage

目的观察经不同途径移植人脐血单核细胞14天后脑出血大鼠神经功能评分的变化,探讨干细胞移植的最佳途径。方法采用自体血二次注血/退针法制作脑出血模型,经计算机断层扫描(computed tomography,CT)检查证实脑出血模型构建成功后,将从人脐血中分离出的新鲜人脐血单核细胞(human umbilical cordblood mononuclear cells,HUCBMC)分别经Wistar大鼠尾静脉、左心室及脑出血局部移植入实验动物体内,对照组造模成功后,不予治疗,自然转归。各组模型均于移植1、3、7、14天采用Longa评分法评价大鼠神经功能。结果经尾静脉、左心室及脑出血局部移植HUCBMC的大鼠神经功能评分,经统计学处理后提示不同时间点大鼠的神经功能评分差异有显著性(F=131.87,P<0.001);移植时间(time)与移植方法(group)的交互效应显示不同的治疗方法时间趋势相同(F=35.54,P>0.05)。大鼠神经功能评分组间比较显示,不同移植方法对大鼠神经功能评分变化的差异有显著性(F=6.434,P=0.001);HUCBMC移植术后1天脑局部移植组大鼠神经功能评分(2.35±0.67)高于其他组,移植术后3、7、14天脑局部移植组大鼠神经功能评分(分别为0.40±0.60,0.25±0.37,0.03±0.22)低于其他组;HUCBMC移植后1天4组大鼠神经功能评分差异无显著性(F=2.14,P=0.1 0);移植3、7、14天4组大鼠神经功能评分差异有显著性(F值分别为5.59,22.94,11.07,其对应P值均<0.01);相同移植途径不同时间点多个样本均数之间比较各组差异有显著性(F值分别为27.71,29.07,92.11,13.47,其对应P<0.001);尾静脉与左心室移植组各时间点神经功能评分差别无显著性(P分别为0.85,0.08,0.70,0.68)。结论经尾静脉、左心室及脑出血局部途径移植人脐血单核细胞治疗脑出血大鼠神经功能均有改善;脑局部移植是脐血单核细胞移植的最佳途径。

Objective To observe the changes in behavior in rats with cerebral hemorrhage which were transplanted human umbilical cord blood stem cells by different ways in two weeks and to discuss the best pathway of stem cell transplanted. Methods An animal model of intracerebral hemorrhage(ICH) was established by autologous blood injection/withdraws two times.The success of cerebral hemorrhage model confirmed by computed tomography(CT) examination.And then fresh human umbilical cord blood mononuclear cells(HUCBMC) which were isolated from human umbilical cord blood were transplanted into experimental animal in vivo respectively by Wister rats,caudal vein,left ventricular and the position of cerebral hemorrhage.The control group was fed well without treatment after modeling successfully and observed the process of natural recovery.The behavior of each model was assessed by Longa 5 grading method on 1,3,7 and 14 days. Results Statistical data suggested that it was a significant difference in the changes of rats. neurological function at different time points which were transplanted HUCBMC through the tail vein,left ventricular and cerebral hemorrhage local path ways(F= 131.87,P<0.001).The factors which time and group interaction effect showed that different treatment tend to the same trends of time(F=35.54,P>0.05).Influence of different transplantation methods on changes of neural function in rats was different(F=6.434,P=0.001).The rats,neurological function scores(2.35±0.67) which were transplanted HUCBMC by cerebral hemorrhage local pathways were obviously higher than the other groups on the 1st day.And the scores(0.40±0.60,0.25±0.37,0.03±0.22) were lower than the other groups on the 3th,7th and 14th days.There was no significant differences between the neurological function scores of the four groups when HUCBMC were transplanted for 1 day(F=2.14,P=0.10).There were significant differences between the group transplanted by the local cerebral group and the other groups on the 3th,7th and 14th days(F=5.59,22.94 and 11.07,All of P<0.01).There were no significant differences between the group transplanted by caudal vein and left ventricular(P=0.85,0.08,0.70,0.68). Conclusion Human umbilical cord blood stem cell transplantation can improve the neural function in rats with cerebral hemorrhage through the tail vein,left ventricular and cerebral hemorrhage local pathway.The best way of transplantation was local cerebral transplantation.