CAJ | 학술논문

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.
목적 탐토인제혈간충질간세포(HUCBMSCs)이식대뇌손상대서적면역조절화뇌보호작용궤제,위뇌손상적간세포치료제공의거.방법 용Brdu표기적HUCBMSCs경서미정맥식입대서창상성뇌손상모형.채용NSS방법행신경손상엄중정도평분.정상조불작임하처리,재조모후제1천、제2천、제3천、제5천화제7천검측화비교가상조、손상조화이식조대서혈청면역지표적변화(염증개질、전혈재지다당자격후합성TNF-α적능력).결과 Brdu양성적MSCs재이식조대서뇌손상주변구명현취집.제제1천외,각시간점이식조대서신경공능득분교손상조강저,차이유통계학의의(t=3.35、5.70、5.40、4.93,P균＜0.05).이식조대서재손상후각개시간점혈청IL-6수평교손상조현저강저(t=4.72、3.53、3.77、2.32、2.43,P균＜0.05),재손상후제1천혈청IL-8수평교손상조현저강저(t=2.26,P＜0.05),이이식조IL-10경력단잠하강후출현명현적회승추세,재후기(제5천화제7천)혈청IL-10수평심지고우가상조(t=2.61、2.81,P균＜0.05).이식조대서전혈체외합성TNF-α능력재손상조기수연출현신속하조,단중후기가이관찰도저개지표상조적추세,균고우동시간점손상조대서수평(t=2.12、2.53、2.77、4.32、7.43,P균＜0.05).결론 미응용면역억제제적정황하,경미정맥주사HUCBMSCs가천이지면역공능건전적대서뇌창상조주변구,HUCBMSCs능강저엄중창상적고염성반응,병유효뉴전창상후적면역억제상태,유조우신경공능개선.
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 neurons.