基质金属蛋白酶-2、9及组织金属蛋白酶抑制物-1与脑小血管病患者脑白质高信号的相关性研究  

Correlations of matrix metalloproteinase-2,matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 with white matter hyperintensities in patients with cerebral small vessel disease

作　　者：罗贝琳 张艺芬 何顺坡 朱仁敬[2] 阳清伟 郑玉琴[2] 黄富治 苏华妹 LUO Beilin;ZHANG Yifen;HE Shunpo;ZHU Renjing;YANG Qingwei;ZHENG Yuqin;HUANG Fuzhi;SU Huamei(The Graduate School of Fujian Medical University,Fuzhou,Fujian 350000,P.R.China;Department of Neurology,Zhongshan Hospital,Xiamen University,Xiamen,Fujian 361000,P.R.China)

机构地区：[1]福建医科大学研究生院,福州350000 [2]厦门大学附属中山医院神经内科,福建厦门361000

出　　处：《华西医学》2024年第5期723-731,共9页West China Medical Journal

基　　金：厦门市医疗卫生指导性项目(3502Z20214ZD1047)。

摘　　要：目的探讨血清基质金属蛋白酶(matrix metalloproteinase,MMP)-2、MMP-9、组织金属蛋白酶抑制物-1(tissue inhibitor of metalloproteinase-1,TIMP-1)及其比值与脑小血管病(cerebral small vessel disease,CSVD)患者脑白质高信号(white matter hyperintensity,WMH)严重程度的相关性。方法前瞻性纳入2022年1月—2024年2月于厦门大学附属中山医院就诊的CSVD患者,采用Fazekas分级和病灶预测算法对WMH进行定性和定量分析。测定MMP-2、MMP-9、TIMP-1等生物标志物,探索它们与WMH严重程度的相关性。结果共纳入CSVD患者144例,其中男63例,女81例,年龄(67.60±8.73)岁。WMH Fazekas 1、2、3级的患者分别有83例(57.6%)、41例(28.5%)、20例(13.9%),WMH中位总体积4.31 mL。Fazekas分级的无序多分类logistic回归分析(以1级为参照)结果显示,MMP-2[2级:比值比(odds ratio,OR)=1.059,95%置信区间(confidence interval,CI)(1.016,1.105);3级:OR=1.463,95%CI(1.124,1.905)]、TIMP-1[2级:OR=1.019,95%CI(1.006,1.032);3级:OR=1.048,95%CI(1.008,1.090)]、MMP-9/TIMP-1[3级:OR=2.650,95%CI(1.393,5.039)]与Fazekas分级独立相关(P<0.05)。WMH总体积四分位数分组的无序多分类logistic回归分析(以Q1组为参照)结果显示,MMP-2[Q2组:OR=1.160,95%CI(1.021,1.318);Q3组:OR=1.238,95%CI(1.086,1.412);Q4组:OR=1.313,95%CI(1.140,1.512)]、TIMP-1[Q2组:OR=1.095,95%CI(1.054,1.138);Q3组:OR=1.084,95%CI(1.045,1.125);Q4组:OR=1.102,95%CI(1.057,1.149)]与WMH四分位数分组独立相关(P<0.05)。结论血清MMP-2、TIMP-1水平与Fazekas分级及WMH总体积均独立相关,它们与CSVD WMH严重程度的关联性,提示它们作为疾病相关生物指标的潜力。Objective To explore the correlations of serum levels of matrix metalloproteinase(MMP)-2,MMP9,tissue inhibitor of metalloproteinase-1(TIMP-1),and their ratios,with the severity of white matter hyperintensities(WMH)in patients with cerebral small vessel disease(CSVD).Methods This prospective study included patients with CSVD who were treated at Zhongshan Hospital,Xiamen University between January 2022 and February 2024.Qualitative and quantitative analyses of WMH were performed using the Fazekas scale and lesion prediction algorithm.Biomarkers such as MMP-2,MMP-9,and TIMP-1 were measured to explore their correlations with the severity of WMH.Results A total of 144 patients with CSVD were included in this study, comprising 63 males and 81 females, with an average age of(67.60±8.73) years. There were 83 (57.6%), 41 (28.5%), and 20 (13.9%) patients were categorized as Fazekas grade 1, 2, and3 for WMH, respectively, with an median total WMH volume of 4.31 mL. Multinomial logistic regression analysis forFazekas grade (grade 1 as the reference level) showed that MMP-2 [grade 2: odds ratio (OR)=1.059, 95% confidenceinterval (CI) (1.016, 1.105);grade 3: OR=1.463, 95%CI (1.124, 1.905)], TIMP-1 [grade 2: OR=1.019, 95%CI (1.006, 1.032);grade 3: OR=1.048, 95%CI (1.008, 1.090)], and MMP-9/TIMP-1 [grade 3: OR=2.650, 95%CI (1.393, 5.039)] wereindependently associated with Fazekas grade (P<0.05). Multinomial logistic regression analysis for the quartile group oftotal WMH volume (group Q1 as the reference level) showed that MMP-2 [group Q2: OR=1.160, 95%CI (1.021, 1.318);group Q3: OR=1.238, 95%CI (1.086, 1.412);group Q4: OR=1.313, 95%CI (1.140, 1.512)] and TIMP-1 [group Q2: OR=1.095,95%CI (1.054, 1.138);group Q3: OR=1.084, 95%CI (1.045, 1.125);group Q4: OR=1.102, 95%CI (1.057, 1.149)] wereindependently associated with the quartile group of total WMH volume (P<0.05). Conclusions     Serum levels of MMP-2and TIMP-1 demonstrate significant independent associations with both the Fazekas grade and the total volume of WMHin patients

关 键 词：基质金属蛋白酶 组织金属蛋白酶抑制物 脑小血管病 脑白质高信号 头颅磁共振成像 

分 类 号：R74[医药卫生—神经病学与精神病学]