人脐带间充质干细胞移植对新生大鼠缺氧缺血性脑损伤的保护作用  

Intracerebral transplantation of human umbilical cord-derived mesenchymal stem cells in neonatal rat model of hypoxic-ischemic brain damage: protective effect to injured brain

作　　者：张德双[1,2] 白小红[1] 陈大鹏[1] 母得志[1] 陈娟[1] 

机构地区：[1]四川大学华西第二医院新生儿科,四川成都610041 [2]泸州医学院附属医院新生儿科,四川泸州646000

出　　处：《中国当代儿科杂志》2014年第9期927-932,共6页Chinese Journal of Contemporary Pediatrics

摘　　要：目的探讨人脐带间充质干细胞(hUC-MSCs)对新生大鼠缺氧缺血性脑损伤(HIBD)的保护作用及可能机制。方法 10日龄Sprague-Dawley大鼠随机分为假手术组、HIBD组和MSCs组,建立新生大鼠HIBD模型,建模后24 h MSCs组侧脑室注入hUC-MSCs。移植后24、48 h应用TUNEL及Western blot分别检测细胞凋亡及Caspase-3的表达;移植后1、2、3周应用Longa评分评价大鼠的神经行为,免疫荧光观察hUCMSCs的存活、分化情况。结果移植后24、48 h,MSCs组大鼠的细胞凋亡及Caspase-3的表达较HIBD组减少(P<0.05);移植后2、3周,MSCs组Longa评分低于HIBD组(P<0.05);移植后脑组织中可见BrdU阳性细胞;MSCs组胶质纤维酸性蛋白(GFAP)及神经元特异烯醇化酶(NSE)阳性表达高于HIBD组及假手术组(P<0.05),随时间延长其表达逐渐增强(P<0.05)。结论 hUC-MSCs移植治疗新生大鼠HIBD时,早期可抑制Caspase-3的表达,减少细胞凋亡;后期存活的hUC-MSCs可分化为神经样细胞,并促进内源性神经样细胞的分化,发挥脑保护作用。Objective To study the brain protection and the possible mechanism of human umbilical cord-derived mesenchymal stem cells（hUC-MSCs） in neonatal rat model of hypoxic-ischemic brain damage（HIBD）. MethodsSuccessfully establishing a neonatal rat model of HIBD, hUC-MSCs labeled with BrdU were transplanted into the lateral ventricle 24 hours after HIBD. The number of apoptotic cells and the expression of Caspase-3 were detected by TUNEL and Western blot respectively at 24 and 48 hours after transplantation. The neurological functions of HIBD rats were evaluated by Longa score, and the survival, differentiation and pro-differentiation effects of hUC-MSCs were identified by immunofluorescence at 1 to 3 weeks after transplantation. Results At 24 and 48 hours after transplantation, apoptotic cells and Caspase-3 expression in the MSCs group were less than in the HIBD group（P〈0.05）. At 2 and 3 weeks after transplantation, the Longa score in the MSCs group was lower than in the HIBD group（P〈0.05）. After transplantation, positive cells labeled with BrdU were seen in the brain tissue. The expression levels of glial fibrillary acidic protein（GFAP） and neuron specific esterase（NSE） in the MSCs group were higher than in the HIBD and shamoperated control groups（P〈0.05）, and increased gradually with the transplantation time（P〈0.05）. Conclusions hUCMSCs transplantation in HIBD rats can inhibit Caspase-3 expression and reduce apoptotic cells in the early stage, and in the later period, the survival hUC-MSCs can differentiate into neural-like cells and promote the differentiation of endogenous neural-like cells, providing protective effects to brain.

关 键 词：人脐带间充质干细胞 移植 缺氧缺血性脑损伤 凋亡 新生大鼠 

分 类 号：R722.1[医药卫生—儿科]