动脉瘤性蛛网膜下腔出血患者脑脊液中可溶性血小板源性生长因子受体β与脑血管痉挛的相关性研究

发布时间：2018-03-01 01:34

本文关键词： 蛛网膜下腔出血脑血管痉挛血小板源性生长因子脑脊液　出处：《南方医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究背景:蛛网膜下腔出血(subarachnoid hemorrhage,SAH)是高致残率和致死率的疾病,脑血管痉挛(cerebral vasospasm,CVS)是其主要的并发症。有关CVS发生的确切机制目前尚不清楚。因此有必要对CVS进行进一步研究。血小板源性生长因子(PDGF)是生长因子超家族中的一员,与之结合的受体有PDGFR-a和-β两个亚型。通常情况下,单体状态下的PDGF和PDGFR并无生物学活性。PDGFR各亚型之间结构和功能相似,均有一个胞外域、跨膜域和一个胞内的酪氨酸激酶结构域,对跨膜信号进行转导,对小血管的形成和伤口的修复具有着重要的调节作用。根据既往临床及基础研究提示sPDGFR可能会参与SAH后血管痉挛的发生。方法:本次研究包括2015年11月至2016年4月因动脉瘤性蛛网膜下腔出血入住我院神经外科的患者。所有患者于SAH后1-3d、4-6d、7-9d行腰椎穿刺术留取脑脊液3ml,或者从留有脑室外引流管或者腰椎穿刺引流管处留取3ml脑脊液。对照组于接受椎管内麻醉前留取脑脊液1ml。所有脑脊液sPDGFR的浓度均有酶联免疫吸附试验(ELISA)测得。记录患者年龄、性别、发病时间等一般资料,患者的临床资料(Hunt-Hess分级、Fisher分级、世界神经外科(WFNS)评分)以及患者影像学资料。结果:本研究共纳入32例SAH患者,其中女性20例,男性12例。5例正常人脑脊液作为对照。患者的平均年龄55.7± 12.3岁。SAH后1-3d,患者脑脊液中sPDGFRβ的平均浓度886.93 pg/ml。正常对照组的脑脊液中sPDGFRβ平均浓度484.04 pg/ml。SAH患者脑脊液中平均sPDGFRβ浓度高于正常对照组,差异有统计学意义(p=0.0012)。SAH后患者脑脊液样本(1-3天,4-6天,and 7-9天)中,sPDGFR β的浓度随时间的变化,直到7-9天达到高(886.93±242.86 pg/ml vs 1229.07±513.69 pg/ml vs 1338.13±468.30 pg/ml,p0.001)。ROC曲线分析后发现1-3dsPDGFR β浓度对脑血管痉挛有一定的预测能力。曲线下面积(AUC)是0.680(p=0.082)。sPGFR β浓度的诊断阈值是975.38 pg/ml。将患者分为两组-血管痉挛组和非血管痉挛组,发现发生脑血管痉挛患者脑脊液中sPDGFRβ浓度明显高于非血管痉挛组,差异有统计学意义(973.46±239.23pg/ml vs 788.85±213.99pg/ml,p=0.029),sPDGFRβ浓度与血管痉挛有明显的相关性(Chi-square=5.542,p=0.019,r=0.416,p=0.018)。SAH 后1-3d脑脊液中高sPDGFRβ浓度是血管痉挛发生的独立危险因素(p=0.001,OR=19.22,95%CI:3.27-113.03),除此之外,年龄(p0.001,OR=0.024,95%CI:0.004-0.157)和 WFNS分级IV-V(p=0.061,OR=5.196,95%CI:1-29.16)也是CVS发生的独立危险因素。脑脊液中高sPDGFRβ浓度不是SAH患者6个月预后不良的独立危险因素。结论:SAH后脑脊液中sPDGFR β浓度明显升高,1-3d脑脊液中高sPDGFR β浓度与SAH后脑血管痉挛的发生明显相关,且是脑血管痉挛发生的独立危险因素。因此,早期检测脑脊液中sPDGFRβ浓度对脑血管痉挛的诊断具有潜在临床参考价值。
[Abstract]:Background: subarachnoid hemorrhage (SAH) is a disease with high disability rate and mortality. Cerebral vasospasmCVS is a major complication of cerebral vasospasm. The exact mechanism of CVS is not clear. Therefore, it is necessary to further study CVS. PDGF is a member of the superfamily of growth factors. The binding receptors are PDGFR-a and 尾 subtypes. In general, PDGF and PDGFR in monomer state have no biological activity. The structure and function of each subtype of PDGFR are similar, and each of them has an extracellular domain. Transmembrane domain and an intracellular tyrosine kinase domain transduction of transmembrane signal. SPDGFR may be involved in the development of vasospasm after SAH according to previous clinical and basic studies. Methods: this study includes November 2015 to 2016. Patients admitted to neurosurgery department for aneurysm subarachnoid hemorrhage. All patients received lumbar puncture at 1-3 d 4-6 d after SAH for 3 ml of cerebrospinal fluid, or 3 ml of brain from left ventricular drainage tube or lumbar puncture drainage tube. Spinal fluid. Cerebrospinal fluid (CSF) 1 ml was retained in the control group before being anesthetized into the spinal canal. The concentration of sPDGFR in all cerebrospinal fluid was measured by enzyme linked immunosorbent assay (Elisa). Sex, onset time and other general data, clinical data of patients with Hunt-Hess grade and Fisher grade, World Neurosurgery WFS score) and imaging data of patients. Results: 32 patients with SAH were included in this study, 20 of whom were women. The average age of patients was 55.7 卤12.3 years. The average concentration of sPDGFR 尾 in CSF was 886.93 PG / ml. The average concentration of sPDGFR 尾 in CSF of normal controls was 484.04 pg/ml.SAH. The concentration was higher than that in the control group. There was a significant difference in the concentration of sPDGFR 尾 with time in cerebrospinal fluid (CSF) samples of patients with SAH (1-3 days, 4-6 days and 7-9 days). By 7 to 9 days after reaching a high level of 886.93 卤242.86 pg/ml vs 1229.07 卤513.69 pg/ml vs 1338.13 卤468.30 PG / ml P 0.001U, ROC curve analysis showed that the concentration of 1-3dsPDGFR 尾 could predict cerebral vasospasm to some extent, and the area under the curve was 0.680p0.082n.sPGFR 尾 concentration, the diagnostic threshold was 975.38 PG / ml. Spastic group and non-vasospasm group, It was found that the concentration of sPDGFR 尾 in cerebrospinal fluid of patients with cerebral vasospasm was significantly higher than that of non-vasospasm group. The difference was statistically significant (973.46 卤239.23 PG / ml vs 788.85 卤213.99pg / ml / ml / ml / ml respectively) and there was a significant correlation between the concentration of sPDGFR 尾 and vasospasm. In addition, the high concentration of sPDGFR 尾 in cerebrospinal fluid was an independent risk factor for the development of vasospasm. In addition, high sPDGFR 尾 concentration in cerebrospinal fluid was found to be an independent risk factor for the development of vasospasm. Age (p 0.001) and WFNS grade IV-V: 0.061) are also independent risk factors for the occurrence of CVS. High sPDGFR 尾 concentration in cerebrospinal fluid is not an independent risk factor for poor prognosis in patients with SAH at 6 months. Conclusion the concentration of sPDGFR 尾 in cerebrospinal fluid is significantly higher than that in cerebrospinal fluid for 1 to 3 days after CVS. The moderate and high concentration of sPDGFR 尾 was significantly correlated with the occurrence of cerebral vasospasm after SAH. Therefore, early detection of sPDGFR 尾 concentration in cerebrospinal fluid has potential clinical reference value in the diagnosis of cerebral vasospasm.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.35

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