成年烟雾病患者血清血管细胞黏附分子1、基质金属蛋白酶9、转化生长因子β、血管内皮生长因子水平变化及其临床意义研究

Changes and Clinical Significance of Serum Levels of VCAM-1,MMP-9,TGF-βand VEGF in Adult Patients with Moyamoya Disease

背景目前,烟雾病(MMD)的病因及发病机制尚不完全明确,此类患者通常在发生脑血管事件后才被确诊,因此探讨MMD的预测因子及评估其严重程度的指标具有重要的临床意义。目的探讨成年MMD患者血清血管细胞黏附分子1(VCAM-1)、基质金属蛋白酶9(MMP-9)、转化生长因子β(TGF-β)、血管内皮生长因子(VEGF)水平及其临床意义。方法选取2016年3月-2019年1月四川大学华西广安医院收治的成年MMD患者114例作为病例组,其中缺血型68例,出血型46例;另选取同期在本院门诊健康体检中心体检健康者30例作为对照组。比较对照组受试者体检当日与病例组患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平,比较出血型与缺血型患者入院第1、7、14天血清VCAM-1、MMP-9、TGF-β、VEGF水平,并比较不同Suzuki分级成年MMD患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平;成年MMD患者入院第1天血清VCAM-1、MMP-9水平与血清TGF-β、VEGF水平的相关性分析采用Pearson相关分析。结果病例组患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平高于对照组(体检当日)(P<0.05)。时间与方法在血清VCAM-1、MMP-9水平上不存在交互作用(P>0.05),在血清TGF-β、VEGF水平上存在交互作用(P<0.05);时间在血清VCAM-1、MMP-9、TGF-β、VEGF水平上主效应显著(P<0.05);方法在血清VCAM-1、MMP-9水平上主效应不显著(P>0.05),在血清TGF-β、VEGF水平上主效应显著(P<0.05);出血型患者入院第1、7、14天血清TGF-β、VEGF水平高于缺血型患者(P<0.05)。Suzuki分级3级缺血型患者血清入院第1天MMP-9、VEGF水平高于Suzuki分级2级患者,Suzuki分级3级出血型患者入院第1天血清VEGF水平高于Suzuki分级2级患者(P<0.05);Suzuki分级4级缺血型、出血型患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平分别高于Suzuki分级2、3级缺血型、出血型患者(P<0.05);Suzuki分级5、6级缺血型、出血型患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平分别高于Suzuki分级2、3、4级缺血型、出血型患者(P<0.05);Suzuki分级6级缺血型、出血型患者入院第1天血清VEGF水平分别高于Suzuki分级5级缺血型、出血型患者(P<0.05)。Pearson相关分析结果显示,缺血型、出血型MMD患者入院第1天血清VCAM-1、MMP-9水平分别与血清TGF-β、VEGF水平呈正相关(P<0.05)。结论缺血型和出血型成年MMD患者血清VCAM-1、MMP-9、TGF-β、VEGF水平均异常升高,且均与患者病情严重程度相关;血清VCAM-1、MMP-9水平分别与缺血型、出血型MMD患者血清TGF-β、VEGF水平呈正相关,VCAM-1、MMP-9可能参与了成年MMD患者颅内出血过程。

Background Etiology and pathogenesis of moyamoya disease(MMD)are not completely clear so far,such patients usually confirmed after occurrence of cerebrovascular events,therefore,it is of great clinical significance to explore the predictive factors of MMD and evaluation indicators of its severity.Objective To investigate the changes and clinical significance of serum levels of VCAM-1,MMP-9,TGF-βand VEGF in adult patients with MMD.Methods From March 2016 to January 2019,a total of 114 adult patients with MMD from West China Guang’an Hospital,Sichuan University were selected as case group,including 68 cases with ischemic type and 46 cases with hemorrhagic type;meanwhile a total of 30 healthy people underwent physical examination in the Healthy Physical Examination Center were selected as control group.Serum levels of VCAM-1,MMP-9,TGF-βand VEGF were compared between control group(detected on the day for physical examination)and case group(detected on the first day after admission),between patients with ischemic type and hemorrhagic type(detected on the first,seventh and fourteenth day after admission),as well as in patients with different Suzuki grades(detected on the first day after admission);Pearson correlation analysis was used to analyze the correlations of serum levels of VCAM-1 and MMP-9 with serum levels of TGF-βand VEGF in adult patients with MMD.Results Serum levels of VCAM-1,MMP-9,TGF-βand VEGF in case group(detected on the first day after admission)were statistically significantly higher than those in control group(detected on the day for physical examination)(P<0.05).There was no statistically significant interaction on serum level of VCAM-1 or MMP-9 levels between time and method(P>0.05),while there was statistically significant interaction on serum levels of TGF-βand VEGF between time and method(P<0.05);main effects of time were statistically significant on serum levels of VCAM-1,MMP-9,TGF-βand VEGF(P<0.05);main effect of method was not statistically significant on serum level of VCAM-1 or MMP-9(P>0.05),while main effects of method were statistically significant on serum levels of TGF-βand VEGF(P>0.05);serum levels of TGF-βand VEGF in patients with hemorrhagic type were statistically significantly higher than those in patients with ischemic type detected on the first,seventh and fourteenth day after admission(P<0.05).Serum levels of MMP-9 and VEGF in ischemic type patients classifying as Suzuki grade-3 were statistically significantly higher than those in ischemic type patients classifying as Suzuki grade-2 detected on the first after admission(P<0.05),meanwhile serum VEGF level in hemorrhagic type patients classifying as Suzuki grade-3 was statistically significantly higher than that in hemorrhagic type patients classifying as Suzuki grade-2(P<0.05);serum levels of VCAM-1,MMP-9,TGF-βand VEGF both in ischemic and hemorrhagic type patients classifying as Suzuki grade-4 were statistically significantly higher than those both in ischemic and hemorrhagic type patients classifying as Suzuki grade-2 and-3 detected on the first after admission(P<0.05);serum levels of VCAM-1,MMP-9,TGF-βand VEGF both in ischemic and hemorrhagic type patients classifying as Suzuki grade-5 and-6 were statistically significantly higher than those both in ischemic and hemorrhagic type patients classifying as Suzuki grade-2,-3 and-4 detected on the first after admission(P<0.05);serum VEGF level in ischemic and hemorrhagic type patients classifying as Suzuki grade-6 was statistically significantly higher than that in ischemic and hemorrhagic type patients classifying as Suzuki grade-5 detected on the first after admission,respectively(P<0.05).Pearson correlation analysis results showed that,serum level of VCAM-1,MMP-9 was positively correlated with serum level of TGF-β,VEGF both in ischemic and hemorrhagic type patients with MMD detected on the first after admission,respectively(P<0.05).Conclusion Serum levels of VCAM-1,MMP-9,TGF-βand VEGF abnormally increase both in ischemic and hemorrhagic type adult patients with MMD,and the above four are related to the severity of illness;serum level of VCAM-1,MMP-9 is positively correlated with serum level of TGF-β,VEGF both in ischemic and hemorrhagic type patients with MMD,respectively,VCAM-1 and MMP-9 may be involved in the process of intracranial hemorrhage in patients with MMD.