骨髓间充质干细胞移植通过JAK/STAT通路对缺血性脑梗死大鼠Th17/Treg平衡以及神经元炎性和凋亡的影响

BMSCs transplantation regulates Th17/Treg balance,neuron inflammation and neuron apoptosis through JAK/STAT signal pathway in ischemic cerebral infarction

目的探究骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)移植通过JAK/STAT通路对缺血性脑梗死大鼠T辅助细胞17(T help 17cells,Th17)/调节性T细胞(regulatory T cells,Treg)平衡以及神经元炎性和凋亡的影响。方法通过颈动脉结扎构建大鼠脑缺血性脑梗死模型。将30只建模成功的大鼠分为脑梗死组和脑梗死+BMSCs组(n=15)。另取30只健康大鼠分为对照组和BMSCs组(n=15)。颈动脉注射BMSCs剂量为1×10^(5)个(10μl)。检测和比较各组大鼠神经功能、神经元凋亡情况、白细胞介素(interleukin,IL)-6、肿瘤坏死因子(tumor necrosis factor,TNF)-α以及Th17/Treg水平。评估脑组织和T细胞中JAK/STAT通路水平。结果模型组的mNSS评分、凋亡指数、IL-6、TNF-α、Th17水平、Th17/Treg比例、脑组织和T细胞中JAK和STAT mRNA和蛋白水平显著高于对照组和BMSCs组,Treg水平显著低于对照组和BMSCs组(P<0.05)。模型+BMSCs组的mNSS评分、凋亡指数、IL-6、TNF-α、Th17水平(、Th17/Treg比例、脑组织和T细胞中JAK和STAT mRNA和蛋白水平显著低于模型组,Treg水平显著高于模型组(P<0.05)。结论在缺血性脑梗死早期移植BMSCs能够通过抑制JAK/STAT通路调控Th17/Treg平衡,抑制神经元炎性损伤和凋亡。

This study was designed to investigate the effects of bone marrow mesenchymal stem cells(BMSCs)transplantation on T help 17 cells(Th17)/regulatory T cells(regulatory T cells,Treg)balance and the neuron inflammation and apoptosis through JAK/STAT pathway in rats with ischemic cerebral infarction.Firstly,a rat model of cerebral ischemic cerebral infarction was constructed by carotid artery ligation.Thirty successfully modeled rats were divided into cerebral infarction group and cerebral infarction+BMSCs group(n=15),while another 30 healthy rats were divided into control group and BMSCs group(n=15).The dose of BMSCs injected into the carotid artery of experimental rats was 1×10^(5)/10μl.The nerve function,neuronal apoptosis,interleukin(IL)-6,tumor necrosis factor(TNF)-α,and Th17/Treg levels of rats were tested and compared.The level of JAK/STAT pathway in brain tissue and T cells were detected.Data showed that the mNSS score,apoptosis index,IL-6,TNF-α,Th17,Th17/Treg ratio,JAK and STAT mRNA and protein levels in brain tissue and T cells of the model group were significantly higher than those of the control group and BMSCs group,while Treg levels was significantly lower than those of the control group and BMSCs group(P<0.05).All these indicators mentioned above were reversed in model+BMSCs group(P<0.05).In conclusion,transplantation of BMSCs in the early stage of ischemic cerebral infarction regulates Th17/Treg balance by inhibiting the JAK/STAT pathway,thus alleviates neuronal inflammatory damage and apoptosis.