作者：陈捷1 ，程亚玲 2 ，陈海燕 1 ，官念 1

单位：

1.638000 四川省广安市，四川大学华西广安医院神经内科；　2.638000 四川省广安市，四川大学华西广安医院心内科；通信作者：程亚玲，E-mail：14292399@qq.com

关键词：

烟雾病；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；血管增生相关因子

Keywords：

Moyamoya disease；Vascular cell adhesion molecule-1；Matrix metalloproteinase-9； Transforminggrowth factor beta；Vascular endothelial growth factor； Vascular proliferation-related factor

CLC：

R 743.4

DOI：

DOI：10.3969/j.issn.1008-5971.2020.05.006

Funds：

四川省卫生和计划生育委员会科研课题（17PJ090）

摘要：

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。

Abstract：

Background　Etiology and pathogenesis of moyamoya disease（MMD）are not completely clear sofar，such patients usually confirmed after occurrence of cerebrovascular events，therefore，it is of great clinical significance toexplore the predictive factors of MMD and evaluation indicators of its severity. Objective　To investigate the changes and clinicalsignificance of serum levels of VCAM-1，MMP-9，TGF-β and VEGF in adult patients with MMD. Methods　From March2016 to January 2019，a total of 114 adult patients with MMD from West China Guang'an Hospital，Sichuan University wereselected as case group，including 68 cases with ischemic type and 46 cases with hemorrhagic type；meanwhile a total of 30healthy people underwent physical examination in the Healthy Physical Examination Center were selected as control group. Serumlevels of VCAM-1，MMP-9，TGF-β and VEGF were compared between control group（detected on the day for physicalexamination）and case group（detected on the first day after admission），between patients with ischemic type and hemorrhagictype（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 ofVCAM-1 and MMP-9 with serum levels of TGF-β and VEGF in adult patients with MMD. Results　Serum levels of VCAM-1，MMP-9，TGF-β and VEGF in case group（detected on the first day after admission）were statistically significantly higherthan those in control group（detected on the day for physical examination）（P<0.05）.There was no statistically significantinteraction on serum level of VCAM-1 or MMP-9 levels between time and method（P>0.05），while there was statisticallysignificant interaction on serum levels of TGF-β and VEGF between time and method（P<0.05）；main effects of time werestatistically significant on serum levels of VCAM-1，MMP-9，TGF-β and VEGF（P<0.05）；main effect of method wasnot statistically significant on serum level of VCAM-1 or MMP-9（P>0.05），while main effects of method were statisticallysignificant on serum levels of TGF-β and VEGF（P>0.05）；serum levels of TGF-β and VEGF in patients with hemorrhagictype were statistically significantly higher than those in patients with ischemic type detected on the first，seventh and fourteenthday after admission（P<0.05）.Serum levels of MMP-9 and VEGF in ischemic type patients classifying as Suzuki grade-3were statistically significantly higher than those in ischemic type patients classifying as Suzuki grade-2 detected on the firstafter admission（P<0.05），meanwhile serum VEGF level in hemorrhagic type patients classifying as Suzuki grade-3 wasstatistically significantly higher than that in hemorrhagic type patients classifying as Suzuki grade-2（P<0.05）；serum levelsof VCAM-1，MMP-9，TGF-β and VEGF both in ischemic and hemorrhagic type patients classifying as Suzuki grade-4 werestatistically significantly higher than those both in ischemic and hemorrhagic type patients classifying as Suzuki grade-2 and -3detected on the first after admission（P<0.05）；serum levels of VCAM-1，MMP-9，TGF-β and VEGF both in ischemic andhemorrhagic type patients classifying as Suzuki grade-5 and -6 were statistically significantly higher than those both in ischemicand hemorrhagic type patients classifying as Suzuki grade-2，-3 and -4 detected on the first after admission（P<0.05）；serumVEGF level in ischemic and hemorrhagic type patients classifying as Suzuki grade-6 was statistically significantly higher thanthat 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 withserum 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-β and VEGF abnormally increase both inischemic and hemorrhagic type adult patients with MMD，and the above four are related to the severity of illness；serum level ofVCAM-1，MMP-9 is positively correlated with serum level of TGF-β，VEGF both in ischemic and hemorrhagic type patientswith MMD，respectively，VCAM-1 and MMP-9 may be involved in the process of intracranial hemorrhage in patients withMMD.

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