王芳,杨科,朱梦霞,黄靓,邹飞燕,王汉群.骨髓间充质干细胞移植对缺血性脑卒中大鼠炎症因子的影响.[J].中南医学科学杂志.,2021,(5):506-511.
骨髓间充质干细胞移植对缺血性脑卒中大鼠炎症因子的影响
Effect of BMSC transplantation on inflammatory factors in inchemic stroke rats
投稿时间:2021-04-10  修订日期:2021-06-17
DOI:10.15972/j.cnki.43-1509/r.2021.05.003
中文关键词:  骨髓间充质干细胞  缺血性脑卒中  大脑中动脉阻塞  神经功能
英文关键词:bone marrow mesenchymal stem cells  cerebral arterial thrombosis  MACO  neurological function
基金项目:湖南省教育厅科学研究项目(17C1396);国家级大学生创新创业训练计划项目(201710555009) 作者简介:王芳,博士研究生,讲师,研究方向为干细胞移植与脑血管疾病,E-mail为514894146@qq.com。通信作者杨科,硕士,讲师,研究方向为肿瘤化学治疗,E-mail为38648174@qq.com。
作者单位
王芳 南华大学 外科学总论教研室,湖南省衡阳市 421001 
杨科 南华大学 诊断学教研室,湖南省衡阳市 421001 
朱梦霞 南华大学 外科学总论教研室,湖南省衡阳市 421001 
黄靓 南华大学 外科学总论教研室,湖南省衡阳市 421001 
邹飞燕 南华大学 外科学总论教研室,湖南省衡阳市 421001 
王汉群 南华大学 外科学总论教研室,湖南省衡阳市 421001 
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中文摘要:
      目的通过骨髓间充质干细胞(BMSC)移植治疗,观察缺血性脑卒中大鼠神经功能恢复情况,检测大鼠神经元凋亡、小胶质细胞激活及炎症因子释放来探讨BMSC神经修复的可能机制。方法24只SD雄性大鼠随机分为空白对照组、模型组和BMSC组。模型组和BMSC组采用改良线栓法制备大鼠大脑中动脉阻塞(MCAO)的缺血再灌注模型,BMSC组造模成功后予以BMSC尾静脉注射。于注射后第28天观察大鼠神经行为学评分,通过实时荧光定量PCR及ELISA检测大鼠血清及脑组织中炎症因子表达水平,用激光共聚焦显微镜观察小胶质细胞的激活,Western blot检测各组脑组织相关蛋白。结果与空白对照组比较,MCAO大鼠神经行为学评分明显升高(P<0.01),血清及脑组织中白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-4(IL-4)、白细胞介素-10(IL-10)及转化生长因子-β1(TGF-β1)的表达明显升高(P<0.001),小胶质细胞激活明显,神经元凋亡增加(P<0.001)。与模型组比较,BMSC组大鼠神经行为学评分降低(P<0.05),血清及脑组织中促炎因子IL-1β、TNF-α和IL-6的表达明显降低(P<0.01),抑炎因子IL-4、IL-10和TGF-β1的表达明显升高(P<0.01),小胶质细胞激活下降,神经元凋亡减轻(P<0.01)。结论骨髓间充质干细胞移植对缺血性脑损伤有部分修复作用,其机制可能与抑制小胶质细胞的激活,抑制过度炎症反应,减轻神经元凋亡有关。
英文摘要:
      To investigate the recovery of neurological function in rats with ischemic stroke by transplantation of bone marrow mesenchymal stem cells (BMSC), and to explore the possible mechanism of neural repair of BMSC by detecting apoptosis, microglia activation and inflammatory factors release. MethodsTwenty-four SD rats were randomly divided into three groups:control group, model group (MCAO group) and experimental group (MCAO+BMSC group). The middle cerebral artery occlusion (MCAO) model was established by modified occlusion method. The control group was not treated. The model group was treated with the same amount of normal saline. BMSC transplantation was performed in the experimental group after successful modeling. The neurobehavioral scores were observed on the 28th day after transplantation. The changes of inflammatory factors were detected by Real-time PCR and ELISA. The activation of microglia was observed by laser confocal microscopy (Confocol), and the apoptosis of brain tissue was detected by Western blot. ResultsCompared with control group, the neurobehavioral scores of MCAO rats were significantly increased (P<0.01), the levels of IL-1β, TNF-α, IL-6, IL-4, IL-10 and TGF-β1 were significantly increased (P<0.001), and microglia activation and apoptosis increased significantly (P<0.001). Compared with MCAO group, the neurobehavioral score of rats in MCAO+BMSC group was significantly decreased (P<0.05), the expressions of pro-inflammatory factors IL-1β, TNF-α and IL-6 were significantly decreased (P<0.01), the expression of anti-inflammatory cytokines IL-4, IL-10 and TGF-β1 were significantly increased (P<0.01), the activation of microglia was decreased and the apoptosis was alleviated (P<0.01). ConclusionBone marrow mesenchymal stem cell transplantation can partially repair ischemic brain injury by inhibiting the activation of microglia and excessive inflammatory response.
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