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急性脑梗死患者外周血内皮祖细胞的水平变化及相关性研究
Changs and Correlation Study of Level of Peripheral Blood Endothelial Progenitor Cells in Patients with Acute Cerebral Infarction
【作者】 程燕;
【导师】 钟平;
【作者基本信息】 安徽医科大学 , 神经病学, 2016, 硕士
【摘要】 目的动态观察急性脑梗死(Acute Cerebral Infarct,ACI)患者外周血内皮祖细胞(endothelial progenitor cells, EPCs)的水平变化,同时检测外周血血管内皮生长因子(vascular endothelial growth factor,VEGF)和基质细胞衍生因子-1(stromal cell-derived factor-1,SDF-1)的含量,以探讨急性脑梗死后EPCs的动员机制,为临床缺血性脑卒中的防治提供新的思路及理论基础。方法选择2015年01月01日至2015年12月31日入住宿州市立医院神经内科首次发病24h内急性脑梗死住院患者50例,同期选择该院体检中心年龄配对的健康体检者40例作为对照组。急性脑梗死患者根据TOAST分型、颈动脉有无斑块及斑块性质进行分组,其中,TOAST分型分为3组:大动脉粥样硬化型(Large artery atherosclerosis,LAA)26例,心源性栓塞型(Cardioembolism,CE)5例,小动脉闭塞型(Small artery occlusion lacunay,SAO)19例;颈动脉有无斑块分为2组:斑块组38例,无斑块组12例;斑块组根据斑块性质分为2组:易损斑块组25例和稳定斑块组13例。以CD133+KDR+细胞作为EPCs的标记,进行流式细胞分析,分别检测急性脑梗死患者发病后第1,5,10d的外周血EPCs数量,同时采用酶联免疫吸附法测定外周血VEGF和SDF-1的含量。EPCs变化率定义为(EPCssd-EPCs1d)与EPCs1d的比值。结果(1)脑梗死组患者外周血EPCs基线数量明显低于对照组(t=-6.046,P<0.001);收缩压、低密度脂蛋白可能是影响急性脑梗死组基线EPCs数量的独立危险因素。(2)脑梗死组患者TOAST各亚型外周血EPCs的基线数量均低于对照组,差异有统计学意义(P<0.05),但TOAST各亚型之间外周血EPCs的基线数量差异无统计学意义(F=0.273,P=0.762)。(3)脑梗死组患者斑块组外周血EPCs基线数量低于无斑块组,差异有统计学意义(P<0.05);易损斑块组外周血EPCs基线数量高于稳定斑块组,差异有统计学意义(P<0.05)。(4)脑梗死组患者外周血EPCs数量于第5d升高,第10d呈下降趋势。(5)脑梗死组患者外周血VEGF、SDF-1含量于第5d升高,第10d呈降低趋势。(6)脑梗死组患者外周血EPCs的变化率与第5d时VEGF、SDF-1含量呈正相关:第5d时VEGF含量与SDF-1含量呈正相关。结论急性脑梗死患者外周血EPCs基线数量较对照组明显降低,EPCs可能是急性脑梗死的一项重要危险因素。EPCs数量与颈动脉有无斑块、斑块性质具有一定相关性,表明EPCs可作为颈动脉粥样硬化及缺血性脑疾病的一项重要指标。急性脑梗死后外周血EPCs数量增加,提示脑缺血后EPCs可从骨髓动员至外周血中。急性脑梗死后外周血EPCs的动员可能与VEGF、SDF-1表达增加有关,三者之间可能相互作用、相互影响,共同参与缺血性脑疾病的血管新生、修复、神经元的保护等过程,对临床估测脑梗死患者的病情、预后具有一定的指导意义,可为缺血性脑卒中的治疗提供一条新途径。
【Abstract】 Objectives:Dynamic observation on the changes of peripheral blood endothelial progenitor cells(EPCs) in patients with acute cerebral infarction(ACI).Meanwhile detecting vascular endothelial growth factor(VEGF) and stromal cell-derived factor(SDF-1) content of the peripheral blood. Further to explore the mechanism of EPCs mobilization of ACI.To provide the new ideas and theoretical basis for the control of ischemic stroke.Methods:50 patients were enrolled with 24 hours of onset of ACI between January 1 and December 31 of 2015 at Department of Neurology,SuZhou Hospital Affiliated to Anhui Medical University.Collecting 40 healthy cases from Medical Examination Center of this hospital at the same time,as a control group.Patients with ACI were grouped according to the TOAST criteria,plaque formation in carotid and plaque feature.TOAST criteria were divided into three group:Large artery atherosclerosis(LAA) group with 26 patients,Cardioembolism(CE) with 5 patients,Small artery occlusion lacunay(SAO) with 19 patients.Plaque formation in carotid were divided into two groups:plaque group with 38 patients and non plaque group with 12 patients.Plaque group were divided into two groups according to plaque feature.Unlnerable plaque group with 25 patients and stable plaque group with 13 patients.The level of EPCs(surface markers:CD133+KDR+) were tested using flow cytometry at day 1,5,10 after ACI.Meanwhile VEGF and SDF-1 content were examined by ELISA.EPCs change rate was defined as(EPCs5d-EPCs1d) and EPCs1d radio.Results:(1)Baseline level of EPCs was significantly lower in patients with ACI than control group.Systolic pressure and LDL were independent risk factors of EPCs Baseline level.(2)Baseline quantities of EPCs was lower in different TOAST criteria than control group,the difference is statistically significant.But the difference between the different EPCs Baseline quantities in different TOAST criteria has no statistical significance.(3)Baseline quantities of EPCs was lower in plaque group than non plaque group.Baseline quantities of EPCs in unlnerable plaque group was higher than stable plaque group.(4) The number of EPCs increased gradually at day 5 and decreased at 10 after ACI.(5)The content of VEGF and SDF-1 increased gradually at day 5 and decreased at 10 after ACI.(6)EPCs change rate was positively correlated with VEGF and SDF-1 content at day 5. VEGF content was positively correlated with SDF-1 content at day 5.Conclusion.Baseline level of EPCs was significantly lower in patients with ACI than control group,EPCs may be an important risk factor for ACI.And quantity shows some coorrelation with plaque formation in carotid and plaque feature, it shows that EPCs can be an important indicator for carotid artery atherosclerosis and ischemic cerebral diseases.The increase of quantity of EPCs after ACI indicate that EPCs mobilization to peripheral blood from bone marrow.The mechanism of EPCs mobilization may associated with expression of VEGF and SDF-1 after ACI.They may affect process of ischemic cerebral diseases together through repairing the damaged vascular and protecting the neurons and so on.This may has guide meaning for estimating the condition and prognosis for ACI.It would provide a new approach for the treatment of ACI.