促血管生成素对动脉瘤性蛛网膜下腔出血预后关系

Angiopoietin affects the prognosis in patients with aneurysmal subarachnoid hemorrhage

目的探讨动脉瘤性蛛网膜下腔出血(a SAH)患者血清促血管生成素(Ang)水平及其对a SAH患者预后的影响。方法采用前瞻性队列研究的方式,收集2015年1月至2016年3月青岛大学第三附属医院青岛市市立医院脑科中心收治的150例符合入组条件的a SAH患者作为研究对象,分别于发病后8 h、24 h、72 h采集患者外周静脉血,采用酶联免疫吸附法(ELISA)检测血清促血管生成素-1(Ang-1)、促血管生成素-2(Ang-2)、促血管生成素受体-2(Tie-2)水平,并将该院体检中心同期150例健康成年人的血清Ang水平作为对照;采用重复测量方差分析,比较不同预后a SAH患者血清Ang水平及变化趋势,采用Logistic回归模型分析血清Ang水平与患者预后结局之间的关系。结果a SAH患者血清Ang-1、Ang-2和Tie-2表达水平以及Ang-1/Ang-2比值随着发病时间的延长均呈现不同程度的增高,均高于健康对照组(P<0.05);Ang-1水平和Ang-1/Ang-2比值在发病后8 h内已显著高于健康对照组水平,差异均有统计学意义(P<0.05)。预后良好组a SAH患者血清Ang-1表达水平在SAH后8 h、24 h和72 h均高于预后不良组,血清Ang-2水平在SAH后72 h高于预后不良组,特异性受体Tie-2水平在SAH后24 h高于预后不良组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析显示,SAH发病后8 h、24 h和72 h血清Ang-1表达水平[相对危险度(OR)及95%置信区间(CI)分别为:1.128(0.742~1.714)、2.042(1.151~3.623)、3.893(2.318~6.536)]和SAH后24 h特异性受体Tie-2水平[OR:2.400(1.053~5.474)]是a SAH患者预后的影响因素。结论 a SAH患者血清Ang-1水平变化水平与预后呈正相关关系,预后良好a SAH患者的发病后72 h的血清Ang-1保持较高水平,Ang-1可作为判断a SAH患者预后的重要生物标志物。

Objective The changes of Angiopoietins（Ang） level in patients with aneurysmal subarachnoid hemorrhage（a SAH） were analyzed,and the clinical value of Angiopoietins（Ang） level for evaluating prognosis in patients was investigated. Methods A prospective cohort study was adopted to collect 150 cases of aneurysmal subarachnoid hemorrhage（ a SAH） patients admitted to the Third Affiliated Hospital of Qingdao University from January 2015 to March 2016 as the research object. Blood samples from 150 a SAH patients were collected at 8 h,24 h,72 h after an onset of SAH. The serum levels of Angiopoietin-1（Ang-1）,Angiopoietin-2（Ang-2） and Tyrosine Kinase Receptors-2（Tie-2） were measured by enzyme linked immunosorbent assay（ ELISA）,and angiopoietins levels of 150 healthy adults as control group. Repeated measures analysis of variance was used to compare different angiopoietins levels and trends in different prognosis group patients,and a Logistic regression model was used to analyze the relationship between the level of angiopoietins and prognosis outcome. Results The serum Ang-1,Ang-2 and Tie-2 expression level and Ang-1/Ang-2 ratio of a SAH patients with the prolongation of the time of onset showed varying increasing degrees,which were significantly higher than those in healthy control group（P〈0. 05）. Ang-1 levels and Ang-1/Ang-2 ratio after the onset within 8 h was significantly higher than those of healthy control group（P〈0.05）. The serum Ang-1 expression level in SAH after 8 h,24 h and 72 h in a SAH patients with good prognosis were higher than those with the poor prognosis group; serum Ang-2 levels in SAH after 72 h in good prognosis group were better than those of poor prognosis group; the specific receptor Tie-2 levels in SAH after 24 h was higher than that of the poor prognosis group; the differences were statistically significant（ P〈0. 05）. Multivariate Logistic regression analysis showed that after the onset of SAH 8 h,24 h and 72 h the serum Ang-1 expression level [odd ratio（OR）（95% confidence interval） were： 1.128（0.742 ~1. 714）,2. 042（1. 151 ~3. 623）,3. 893（2. 318 ~6. 536）]and SAH after 24 h specific tyrosine kinase receptor Tie-2 levels [OR： 2. 400（1. 053 ~5. 474）]were the influencing factors of the a SAH patients. Conclusion The serum Ang-1 level change trend of the a SAH patients is positively correlated with the prognosis. Abnormal levels of angiopoietins may affect the early brain injury after SAH and Ang-1 can be used as an important biomarker to detect the prognosis of a SAH.