PI3K/Akt信号通路对脐血间充质干细胞减轻缺血性脑损伤和炎症反应的调节作用  

Regulation effect of PI3K/Akt signaling pathway on umbilical cord blood mesenchymal stem cells in alleviating ischemic brain injury and inflammatory response

作　　者：陈慧[1] 郑晓梅(指导) 夏晓[1] 孙玉锦[1] 徐静[1] CHEN Hui;ZHENG Xiao-Mei;XIA Xiao;SUN Yu-Jin;XU Jing(Department of Neurology,Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)

机构地区：[1]雅安职业技术学院,雅安625000 [2]西南医科大学附属医院神经内科,泸州646000

出　　处：《中国免疫学杂志》2021年第2期155-160,共6页Chinese Journal of Immunology

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.

关 键 词：脐血间充质干细胞 缺血性脑损伤 PI3K/AKT信号通路 

分 类 号：R743[医药卫生—神经病学与精神病学]