人脐血间充质干细胞移植对脑创伤大鼠的免疫调节研究  

Immune response of traumatic brain injury rats regulated by transplantation of human umbilical cord blood mesenchymal stem cells

作　　者：赵俊暕[1] 孟爱国[1] 陈乃耀[1] 王沂[1] 王洋[2] 曾小芳 赵力欣 石峻[1] 

机构地区：[1]河北联合大学附属医院,唐山063000 [2]河北联合大学生命科学院 [3]唐山市第二十二冶医院 [4]不详

出　　处：《国际免疫学杂志》2013年第5期402-407,共6页International Journal of Immunology

基　　金：唐山市科学技术研究与发展计划指令项目（唐山市科技局12150222B-14）

摘　　要：目的 探讨人脐血间充质干细胞（HUCBMSCs）移植对脑损伤大鼠的免疫调节和脑保护作用机制,为脑损伤的干细胞治疗提供依据.方法 用Brdu标记的HUCBMSCs经鼠尾静脉植入大鼠创伤性脑损伤模型.采用NSS方法行神经损伤严重程度评分.正常组不作任何处理,在造模后第1天、第2天、第3天、第5天和第7天检测和比较假伤组、损伤组和移植组大鼠血清免疫指标的变化（炎症介质、全血在脂多糖刺激后合成TNF-α的能力）.结果 Brdu阳性的MSCs在移植组大鼠脑损伤周边区明显聚集.除第1天外,各时间点移植组大鼠神经功能得分较损伤组降低,差异有统计学意义（t=3.35、5.70、5.40、4.93,P均＜0.05）.移植组大鼠在损伤后各个时间点血清IL-6水平较损伤组显著降低（t=4.72、3.53、3.77、2.32、2.43,P均＜0.05）,在损伤后第1天血清IL-8水平较损伤组显著降低（t=2.26,P＜0.05）,而移植组IL-10经历短暂下降后出现明显的回升趋势,在后期（第5天和第7天）血清IL-10水平甚至高于假伤组（t=2.61、2.81,P均＜0.05）.移植组大鼠全血体外合成TNF-α能力在损伤早期虽然出现迅速下调,但中后期可以观察到这个指标上调的趋势,均高于同时间点损伤组大鼠水平（t=2.12、2.53、2.77、4.32、7.43,P均＜0.05）.结论 未应用免疫抑制剂的情况下,经尾静脉注射HUCBMSCs可迁移至免疫功能健全的大鼠脑创伤灶周边区,HUCBMSCs能降低严重创伤的高炎性反应,并有效扭转创伤后的免疫抑制状态,有助于神经功能改善.Object To study the immune effects of intravenous administration of human umbilical cord blood mesenchymal stem cells （HUCBMSCs） on TBI rats,and to explore the mechanisms of neurological recovery.Methods HUCBMSCs were labelled by Brdu before transplantation,the TBI model was established by using modified Feeney free-falling method,and the TBI rats were injected with HUCBMSCs via tail vein.The rats were killed at corresponding time points after evaluating the neurological severity scores （NSS）.On the first,second,third,fifth and seventh days after the rats were traumaed,we detected the values of plasma IL-6,IL-8,IL-10 and TNF-α ex vivo synthesis among the shamed group,the trauma group and the transplanted group,at the same time we compared and analyse the dynamic changes.Results In the transplanted group HUCBM-SCs were found obviously gather around the injured areas.From the NSS scores,we can detect that neurological function of the transplanted group was significantly improved compared with that of trauma group,except the first day （t =3.35,5.70,5.40,4.93,P ＜ 0.05）.In the transplanted group,the amounts of plasma IL-6 were obviously lower than those in trauma group at each time point after trauma （t =4.72,3.53,3.77,2.32,2.43,P ＜ 0.05）.The amounts of plasma IL-8 were obviously lower than those in trauma group on the first day （t =2.26,P ＜0.05）.In the transplanted group both the IL-10 and TNFα decreased for a short period,and then showed an obvious upward trend.In the fifth and seventh days,the amounts of IL-10 were even higher than those in shamed group （t =2.61,2.81,P ＜ 0.05）.And the TNFα exceeded those in trauma group at each time point after trauma （t =2.12,2.53,2.77,4.32,7.43,P ＜ 0.05）.Conclusion With no immuno-suppressants,intravenous-injected HUCBMSCs can migrate to peripheral zone of traumatic brain injury areas of heterogeneous rats,HUCBMSCs can combat hyperinflammation and reverse effectively immunosuppression after trauma and can promote the functional recovery of

关 键 词：人脐血间充质干细胞 创伤性脑损伤 炎性反应 免疫抑制 

分 类 号：R651.1[医药卫生—外科学]