超声造影评估基质金属蛋白酶-9活化调控对颈动脉斑块内新生血管的影响

Contrast-enhanced ultrasound evaluation of the effect of matrix metalloproteinase-9 activation on intraplaque neovessels

目的 应用颈动脉超声造影(CEUS)技术半定量评估斑块内新生血管(IPN),探讨基质金属蛋白酶-9(MMP-9)启动子基因-1562C/T变异、MMP-9与基质金属蛋白酶组织抑制剂-1比值(MMP-9/TIMP-1)对IPN的影响。方法 纳入180例颈动脉粥样硬化斑块患者,应用CEUS评估IPN分级并分组。ELISA法检测血清MMP-9、TIMP-1水平,Sanger法对基因测序;应用相关性分析及logistic回归分析各参数对IPN的影响并绘制ROC曲线。结果 血清MMP-9、MMP-91562C/T变异、MMP-9/TIMP-1比值与IPN超声造影分级呈正相关(r=0.332,r=0.238,r=0.683,P <0.001),logistic回归显示MMP-9/TIMP-1比例失衡是IPN独立危险因素(OR=6.110,95%CI:1.097~34.033,P=0.039),MMP-9/TIMP-1比值≥2.12,IPN超声造影分级≥Ⅲ级的AUC为0.89,敏感度为84.90%,特异度为85.10%。结论 MMP-9酶抑制剂调控MMP-9/TIMP-1比例失衡是IPN独立危险因素。IPN超声造影视觉分级结合MMP-9/TIMP-1比值作适当调整,可较准确评估易损斑块。

Objective To investigate the correlation of matrix metalloproteinase-9(MMP-9)promoter gene-1562C/T mutation,MMP-9/TIMP-1 ratio and intraplaque neovessels(IPN)which were semi-quantitatively assessed by contrast-enhanced ultrasound(CEUS).Methods A total of 180 subjects with carotid atherosclerotic plaques were selected and grouped according to IPN grading.The IPN grading was semi-quantitatively assessed by CEUS.The ELISA measure was utilized to examine serum MMP-9 and TIMP-1 levels.Gene sequence was detected by the Sanger measure.Correlation analysis and logistic regression were employed to analyze the effect of each parameter on IPN,and then receiver operating characteristic(ROC)curve was constructed.Results MMP-9 serum concentration,MMP-91562C/T mutation,MMP-9/TIMP-1 were positively correlated with IPN grading(r = 0.332,r =0.238,r = 0.683,P<0.001).Logistic regression indicated that the imbalance of MMP-9/TIMP-1 proportion was an independent risk factor for IPN(OR = 6.110,95%CI 1.097 ~ 34.033,P = 0.039).If MMP-9/TIMP-1 ≥2.12,the area under ROC curve of IPN grading ≥ Ⅲ was 0.89,the sensitivity was 84.90% and the specificity was85.10%.Conclusion The imbalance of MMP-9/TIMP-1 proportion may be an independent risk factor for IPN.The appropriate adjustment of IPN contrast-enhanced ultrasound visual grading combining with MMP-9/TIMP-1 was beneficial for identification of vulnerable plaques.