摘要
目的:探讨人脐血间充质干细胞(UCBMSCs)对大鼠缺血性脑损伤的保护作用及其对PI3K/Akt信号通路的影响。方法:SD大鼠随机分为假手术组、脑损伤组、VCBMSCs组,术后1、3、7、14 d分别进行神经缺损功能评分、血清炎症因子检测,术后14 d进行脑组织海马区尼氏染色、免疫荧光染色观察人UCBMSCs对缺血性脑损伤的保护作用。另将SD大鼠随机分为假手术组、脑损伤组、UCBMSCs组与UCBMSCs+GSK2141795组(Akt1/2/3抗体抑制剂),术后14 d分别进行脑组织海马部位的Tunel染色与Western blot检测。结果:造模后,脑损伤组大鼠出现明显的神经功能损伤与海马神经元损伤、IL-6水平升高(P<0.05)、转化生长因子β1(TGF-β1)水平降低(P<0.05);UCBMSCs移植减轻缺血性脑损伤大鼠神经功能损伤与海马神经元损伤(P<0.05),IL-6水平降低(P<0.05),TGF-β1水平升高(P<0.05)。大鼠脑海马区可见移植的UCBMSCs,同时可见部分移植细胞分化为神经样细胞;损伤组神经元细胞凋亡率及p-Akt、Bax、IL-6蛋白表达高于假手术组(P<0.05),Bcl-2蛋白表达低于假手术组(P<0.05);UCBMSCs神经元细胞凋亡率及p-Akt、Bax、IL-6蛋白表达低于损伤组(P<0.05),Bcl-2蛋白表达高于损伤组(P<0.05);抑制剂组部分抑制了UCBMSCs的作用。结论:人UCBMSCs可能通过PI3K/Akt信号通路调节炎症反应、减少细胞凋亡,改善缺血性脑损伤的神经功能,发挥神经保护作用。
Objective:To investigate protective effect of human umbilical cord blood mesenchymal stem cells(UCBSCs)on ischemic brain injury in rats and effect on PI3K/Akt signaling pathway.Methods:SD rats were randomly divided into sham group,injury group and UCBMSCs group.Neurological deficit function score and serum inflammatory factors were measured at 1,3,7 and 14 d after operation.Protective effect of human UCBMSCs on ischemic brain injury was observed by Nissl staining and immunofluorescence staining in hippocampus 14 d after operation.SD rats were randomly divided into sham group,injury group,UCBMSCs group.UCBMSCs+GSK2141795 group(Akt1/2/3 antibody inhibitor).Tunel staining and Western blot were used to detect hippocampus of brain tissue 14 d after operation.Results:After establishment of model,obvious neurological impairment and hippocampal neuron injury,increasing IL-6 concentration(P<0.05),decreasing transforming growth factorβ1(TGF-β1)concentration(P<0.05)were observed in injured group,and UCBMSCs transplantation alleviated neurological impairment and hippocampal neuron injury in rats with ischemic brain injury(P<0.05),decreased level of IL-6(P<0.05)and increased TGF-β1 level(P<0.05).Transplanted umbilical cord blood mesenchymal stem cells could be seen in hippocampus of rats,and some of transplanted cells could be differentiated into neuron-like cells.Apoptotic rate and expressions of p-Akt,Bax and IL-6 in injured group were higher than those in sham group(P<0.05),while expression of Bcl-2 was lower than that in sham group(P<0.05);apoptotic rate and expressions of p-Akt,Bax and IL-6 in UCBMSCsl group were lower than those in injured group(P<0.05),and expression of Bcl-2 was higher than that in injured group(P<0.05).UCBMSCs+GSK2141795 group partially inhibited effect of UCBMSCs.Conclusion:Human UCBMSCs may play a neuroprotective role by regulating inflammatory response and reducing apoptosis through PI3K/Akt signaling pathway.
作者
陈慧
郑晓梅(指导)
夏晓
孙玉锦
徐静
CHEN Hui;ZHENG Xiao-Mei;XIA Xiao;SUN Yu-Jin;XU Jing(Department of Neurology,Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2021年第2期155-160,共6页
Chinese Journal of Immunology
