目的:本研究的目的是探讨血清基质金属蛋白酶-2(MMP-2)水平,基质金属蛋白酶-9(MMP-9),以及脑小血管病(CSVD)患者中金属蛋白酶-1(TIMP-1)的组织抑制剂水平及其与白质高信号(WMHs)严重程度的比率。
方法:这项横断面研究是对CSVD患者进行的前瞻性队列研究。使用Fazekas分级和病变预测算法(LPA)方法对WMHs进行定性和定量分析。检测MMP-2、MMP-9和TIMP-1与WMHs病情严重程度的相关性。
结果:样本包括144例CSVD患者。有63名男性和81名女性患者,平均年龄为67.604±8.727岁。其中,58.33%的Fazekas分级为1级的白质高强度,WMHs的平均总模板体积为4.305mL。MMP-2(P=0.025),MMP-9(P=0.008),TIMP-1(P=0.026),根据Fazekas分级,年龄(P=0.007)被确定为WMHs的独立相关因素。WMHs的总模板体积的独立相关性包括MMP-2(P=0.023),TIMP-1(P=0.046),年龄(P=0.047),收缩压(P=0.047),同型半胱氨酸(Hcy)(P=0.014)。此外,年龄(P=0.003;P<0.001),白细胞介素-6(IL-6)(P<0.001;P=0.044),Hcy(P<0.001;P<0.001),糖化血红蛋白(HbA1c)(P=0.016;P=0.043),和慢性肾脏疾病(P<0.001;P<0.001)与WMHsFazekas分级和WMHs的总模板体积有关。
结论:血清MMP-9、MMP-2和TIMP-1水平与Fazekas分级独立相关,而血清TIMP-1和MMP-2水平与WMHs总模板体积独立相关。TIMP-1和MMP-2与CSVD相关WMHs严重程度的相关性表明它们作为疾病相关生物标志物的潜在作用。然而,需要进一步的研究来揭示这些相互作用的具体机制。
OBJECTIVE: The objective of this study was to investigate the correlation between serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels and their ratios with the severity of white matter hyperintensities (WMHs) in patients with cerebral small vessel disease (CSVD).
METHODS: This cross-sectional study was done on a prospective cohort of patients with CSVD. Qualitative and quantitative analyses of WMHs were performed using Fazekas grading and lesion prediction algorithm (LPA) methods. Biomarkers MMP-2, MMP-9, and TIMP-1 were measured to explore their correlation with the severity of WMHs.
RESULTS: The sample consisted of 144 patients with CSVD. There were 63 male and 81 female patients, with an average age of 67.604 ± 8.727 years. Among these, 58.33% presented with white matter hyperintensities at Fazekas grading level 1, with an average total template volume of WMHs of 4.305 mL. MMP-2 (P = 0.025), MMP-9 (P = 0.008), TIMP-1 (P = 0.026), and age (P = 0.007) were identified as independent correlates of WMHs based on Fazekas grading. Independent correlates of the total template volume of WMHs included MMP-2 (P = 0.023), TIMP-1 (P = 0.046), age (P = 0.047), systolic blood pressure (P = 0.047), and homocysteine (Hcy) (P = 0.014). In addition, age (P = 0.003; P < 0.001), interleukin-6 (IL-6) (P < 0.001; P = 0.044), Hcy (P < 0.001; P < 0.001), glycated hemoglobin (HbA1c) (P = 0.016; P = 0.043), and chronic kidney disease (P < 0.001; P < 0.001) were associated with both WMHs Fazekas grading and the total template volume of WMHs.
CONCLUSIONS: Serum levels of MMP-9, MMP-2, and TIMP-1 were independently associated with the Fazekas grading, while serum TIMP-1 and MMP-2 levels were independently related to the total template volume of WMHs. The association of TIMP-1 and MMP-2 with the severity of CSVD-related WMHs suggests their potential role as disease-related biomarkers. However, further research is required to uncover the specific mechanisms underlying these interactions.