脑小血管病认知障碍与血清VEGF及PEDF的相关性研究

Correlation analysis of serum vascular endothelial growth factor levels and pigment epithelial derived factors and vascular cognitive impairment caused by cerebral small-vascular disease

目的:探讨血清血管内皮生长因子(vascular endothelial growth factor,VEGF)及色素上皮衍生因子(pigment epithelial derived factors,PEDF)与脑小血管病(cerebral small-vascular disease,CSVD)认知障碍的关系,为筛查CSVD血管性认知功能障碍(vascular cognitive impairment,VCI)提供有效的生物学标记物。方法:连续性纳入2019年6月至2020年6月包头医学院第一附属医院神经内科住院的CSVD患者,完善患者临床信息资料、3.0 T头颅MRI检查包括T1加权成像、T2加权成像、液体衰减反转恢复序列、弥散加权成像及磁敏感加权成像等相关检查,采用VEGF、PEDF ELISA试剂盒检测血清VEGF、PEDF浓度。应用多变量logistic回归分析确定CSVD认知障碍的独立影响因素,运用SPSS 26.0描绘受试者工作特征(receiver operating characteristic,ROC)曲线,评价血清VEGF、PEDF浓度对CSVD认知障碍的预测价值。结果:①共纳入193例患者,VCI组90例(46.6%),非VCI组103例(53.4%)。2组比较显示,VCI组受教育年限、既往高血压病史、腔隙性梗死或短暂性脑缺血发作史(transient ischemic attack,TIA)、入院收缩压、舒张压、空腹血糖、血肌酐、胱抑素C、血清VEGF浓度、血清PEDF浓度与非VCI组比较,差异有统计学意义(P<0.05)。②运用多变量logistic回归模型分析显示VEGF浓度较高(优势比1.393,95%CI=1.011~1.920,P=0.042)是CSVD认知障碍的独立危险因素;而血清PEDF相对低表达(优势比0.521,95%CI=0.384~0.707,P=0.000)是脑小血管病患者认知功能障碍的独立保护因素;ROC曲线分析显示血清VEGF浓度联合PEDF浓度联合预测脑小血管病认知障碍的曲线下面积为0.769(95%CI=0.705~0.832,P<0.001),敏感性为0.911,特异性为0.612;最佳截断值为128.61 pg/mL、100.95 ng/mL,均具有较好的预测价值。结论:血清VEGF浓度和PEDF浓度与CSVD认知障碍存在显著相关性,血清VEGF浓度联合PEDF浓度可作为CSVD认知障碍的指标。

Objective:To investigate the relationship between vascular endothelial growth factor(VEGF)and pigment epithelial derived factors(PEDF) and cognitive disorder caused by cerebral small-vascular disease(CSVD),so as to provide valuable biomarkers for the early warning screening of vascular cognitive impairment(VCI) caused by CVSD. Methods:Patients with CVSD hospitalized in the Neurology Department of The First Affiliated Hospital of Baotou Medical College from June2019 to June 2020 were continuously enrolled in the study. The relevant clinical data of the patients were collected and 3.0 T cranial MRI examinations were performed on them,including T1-weighted imaging,T2-weighted imaging,fluid attenuated inversion recovery(FLAIR) sequence,diffusion-weighted imaging and susceptibility weighted imaging. Serum VEGF and PEDF level were detected by VEGF and PEDF Elisa Kit. Multivariate logistic regression analysis was used to determine the independent influencing factors of CVSD-caused VCI. SPSS 26.0 was used to describe the receiver operating characteristic(ROC) curve,and the predictive serum VEGF and VEGF level for CVSD-caused VCI was evaluated. Results:A total of 193 patients were enrolled,including 90 patients in VCI group(46.6%)and 103 ones in non-VCI group(53.4%). Compared with non-VCI group,there were significant differences in educational years,past history of hypertension,lacunar infarction or transient ischemic attack(TIA),systolic and diastolic blood pressure,fasting blood glucose,serum creatinine,cystatin-C,serum VEGF and serum PEDF concentrations(P<0.05). Multivariate logistic regression analysis showed that the higher level of serum VEGF(odds ratio:1.393;95%CI=1.011-1.920,P=0.042)was the independent risk factor for VCI in CSVD;and relative lower expression of serum PEDF(odds ratio:0.521,95%CI=0.384-0.707,P=0.000)was the independent protective factor for VCI in CSVD patients. ROC curve analysis showed that the area under the curve of serum VEGF concentration combined with PEDF concentration to predict VCI in CSVD was 0.769(95%CI=0.705-0.832,P<0.001),the sensitivity was 0.911,and the specificity was 0.612. The best cutoff values were 128.61 pg/mL and 100.95 ng/mL,which were of good predictive value. Conclusion:The concentrations of serum VEGF and PEDF are significantly correlated with VCI in CSVD patients,and the levels of serum VEGF and PEDF are expected to serve as the alternative indicators for the assessment of VCI in CSVD.