缺血性脑小血管病与血生物标志物相关研究

Relationship between ischemic cerebral small vessel disease and plasma biomarkers

目的探讨血液中反映炎症、血管内皮功能、凝血功能的生物标志物与脑小血管病间关系。方法前瞻性研究,收集脑小血管病患者265例,根据MRI影像分为腔隙性脑梗死(腔梗)组92例,脑白质病变组113例,腔梗合并脑白质病变(合并)组60例。选择同期门诊、住院或社区体检中心头颅MRI检查未见明显异常的健康体检者65例为对照组。收集一般临床资料,检测各组血管内皮功能指标可溶性细胞间黏附因子1(sICAM-1)、血管性血友病因子(vWF)等血生物标志物水平。采用多重线性回归分析脑小血管病的影响因素。结果与对照组比较,腔梗组、脑白质病变组及合并组高脂血症比例、sICAM-1及vWF水平明显升高(P<0.05,P<0.01)。合并组年龄及D-二聚体水平明显高于对照组[(74.10±7.17)岁vs(70.94±5.26)岁,(1.23±1.11)mg/L vs(0.74±0.68)mg/L,P<0.05],脑白质病变组D-二聚体水平亦明显高于对照组[(1.10±1.03)mg/L vs(0.74±0.68)mg/L,P<0.05]。多重线性回归分析显示,校正年龄等混杂因素,sICAM-1、vWF与脑白质病变严重程度有关(β=125.981,P=0.003;β=49.364,P=0.032)。sICAM-1、vWF与腔隙性脑梗死数量(β=180.329,P=0.000;β=59.095,P=0.012)及脑小血管病严重程度有关(β=230.585,P=0.006;β=51.23,P=0.029)。结论sICAM-1、vWF是影响脑小血管病病情严重程度的独立危险因素,血管内皮细胞功能失调在脑小血管病发展中可能发挥着重要作用。

Objective To study the relationship of plasma biomarkers of inflammation,vascular endothelial function and coagulation with cerebral small vessel disease(CSVD).Methods Two hundred and sixty-five CSVD patients were divided into lacunar cerebral infarction group(n=92),white matter lesion(WML)group(n=113)and lacunar cerebral infarction+WML group(n=60)according to their MRI with 65 persons who underwent physical examination in our hospital during the same period served as a control group.Their general clinical data were recorded.Their serum levels of soluble intracellular adhesion molecule 1(sICAM-1)and von Willebrand factor(vWF)were measured.The influencing factors of CSVD were analyzed by multivariate linear regression analysis.Results The incidence of hyperlipoidemia and serum levels of SICAM-1 and vWF were significantly higher in lacunar cerebral infarction group,WML group and lacunar cerebral infarction+WML group than in control group(P<0.05,P<0.01).The age was significantly older and the serum levels of D-dimer was significantly higher in lacunar cerebral infarction+WML group than in control group(74.10±7.17 years vs 70.94±5.26 years,1.23±1.11 mg/L vs 0.74±0.68 mg/L,P<0.05)and the serum D-dimer level was significantly higher in WML group than in control group(1.10±1.03 mg/L vs 0.74±0.68 mg/L,P<0.05).Multivariate linear regression analysis showed that the serum levels of sICAM-1 and vWF were related with the severity of WML(β=125.981,P=0.003;β=49.364,P=0.032),the number of lacunar cerebral infarctions(β=180.329,P=0.000;β=59.095,P=0.012)and the severity of CSVD(β=230.585,P=0.006;β=51.23,P=0.029).Conclusion SICAM-1 and vWF are the independent risk factors for the severity of CSVD.Vascular endothelial dysfunction plays an important role in the development of CSVD.