静脉移植人脐血单个核细胞治疗脑出血大鼠疗效的microPET-CT评价及抗炎机制

Intravenous transplantation of human umbilical cord blood mononuclear cells in an intracerebral hemorrhage rat model: micro PET-CT evaluation and anti-inflammatory mechanisms

背景:脐血中分离出的单个核细胞含有丰富的细胞类型,在细胞替代治疗、基因治疗以及组织工程学中具有重要的研究和应用价值。目的:通过micro PET-CT及Longa评分评估人脐血单个核细胞治疗大鼠脑出血的疗效,同时探讨其部分治疗机制。方法:采用二次注血/退针法制作脑出血大鼠模型,造模成功大鼠随机分为移植组与对照组,将从人脐血中分离出的单个核细胞经尾静脉注入移植组大鼠体内,对照组大鼠造模成功后不予治疗。各组大鼠均于移植前及移植后的第3,7,14,21天,通过micro PET-CT及Longa评分对大鼠脑代谢变化及神经功能恢复情况进行评估;通过ELISA法检测大鼠血清肿瘤坏死因子α和白细胞介素6的水平。结果与结论:(1)人脐血单个核细胞移植治疗后第7,14,21天,与对照组相比,移植组大鼠血肿中心及血肿周围脑代谢水平均显著升高(P<0.05),血肿及其周围缺血组织体积及Longa评分显著降低(P<0.05);(2)人脐血单个核细胞移植后第3,7,14天,移植组两种因子水平均较对照组显著降低(P<0.05),移植后第21天,两组血清中血清肿瘤坏死因子α和白细胞介素6水平均降至正常水平;(3)结果说明,人脐血单个核细胞移植可促进大鼠脑出血的神经功能恢复,其机制可能与其能够减少炎性因子表达及抑制炎性反应有关。

BACKGROUND:Mononuclear cells isolated from umbilical cord blood(UCB-MNCs)are rich in cell types which are of great benefit in cell replacement therapy,gene therapy and tissue engineering.OBJECTIVE:To evaluate the efficacy of human UCB-MNCs(HUCB-MNCs)in the treatment of intracerebral hemorrhage rats by microPET-CT and Longa scores,and to discuss the therapeutic mechanism.METHODS:We made a rat intracerebral hemorrhage model by autologous blood injection.After modeling,rats were randomly divided into two groups:transplantation group and control group.The HUCB-MNCs were transplanted into the rats in the transplantation group via the tail vein.Control group received no treatment.Before and at 3,7,14,21 days after transplantation,brain metabolic changes and neurological function scores of rats in the two groups were evaluated by microPET-CT and Longa scores.Levels of tumor necrosis factor-αand interleukin-6 in the rat serum of two groups were measured by ELISA method.RESULTS AND CONCLUSION:(1)At 7,14 and 21 days after HUCB-MNCs transplantation,the rates of brain metabolism in the hematoma center as well as around the hematoma in the transplantation group were significantly higher than that in the control group(P<0.05),while the volume of hematoma and surrounding ischemic tissues as well as Longa scores were significantly reduced in the transplantation group as compared with the control group(P<0.05).The levels of tumor necrosis factor-αand interleukin-6 in the serum in the transplantation group were significantly lower than those in the control group at 3,7,14 days after transplantation,and further lowered to the normal levels at 21 days after transplantation.These findings suggest that transplantation of HUCB-MNCs through the tail vein can promote the neurologic recovery of cerebral hemorrhage rats,and one of the therapeutic mechanisms may be related to the reduction of inflammatory factors and the inhibition of inflammatory response.