基质金属蛋白酶-1、9和金属蛋白酶组织抑制因子-1对心房结构重构的作用

Role of matrix metalloproteinases 1 and 9 and tissue inhibitor of metalloproteinase 1 in atrial structural remodeling

目的检测基质金属蛋白酶(MMP)-1、9和金属蛋白酶组织抑制因子(TIMP)-1在风湿性心脏病(风心病)心房颤动(房颤)患者左心房中的表达,探讨其在心房结构重构中的作用。方法选择接受外科换瓣手术的风心病患者43例,其中窦性心律(RSR)组15例,阵发房颤(PAF)组8例,慢性房颤(CAF)组20例。在外科手术中取左心房组织,分别应用免疫印迹法和逆转录-聚合酶链反应测定MMP-1、9和TIMP-1的蛋白含量和mRNA表达量。结果①与RSR组比较,CAF组MMP-9的蛋白水平和mRNA表达均明显增加(P值均<0.01),TIMP-1蛋白水平和mRNA表达均明显降低(P值均<0.01)。各组间MMP-1蛋白水平和mRNA表达的差异均无统计学意义(P值均<0.05)。②CAF组中,MMP-9蛋白水平、mRNA表达与左心房内径(r=0.512、0.500)、房颤持续时间(r=0.927、0.950)均呈正相关(P值均<0.01);TIMP-1则与左心房内径(r=-0.695、-0.401)、房颤持续时间(r=-0.672、-0.695)均呈负相关(P值均<0.01)。TIMP-1与MMP-9蛋白水平和mRNA表达均呈负相关(r值分别=-0.811、-0.655,P值均<<0.01)。结论风心病合并慢性房颤患者的左心房组织中,MMP-9蛋白水平和基因表达均增强,TIMP-1蛋白水平和基因表达则减弱;MMP-9/TIMP-1平衡失调促进心房结构和功能的改变,参与房颤发生和维持。

Objective To detect the expressions of matrix metalloproteinases 1 and 9（MMP-1 and MMP-9） and tissue inhibitor of MMP-1（TIMP-1） in the left atrium of patients with rheumatic heart disease（RHD） complicated with atrial fibrillation（AF）, and to investigate their role in atrial structural remodeling. Methods Forty-three RHD patients undergoing valve replacement were enrolled in this study, including 15 patients with regular sinus rhythm（RSR group）, 8 with paroxysmal AF（PAF group） and 20 with chronic AF（CAF group）. The atrial samples were obtained during surgery for Western blotting to detect the MMP-1, MMP-9 and TIMP-1 protein expressions, and their mRNA expression was detected using reverse transcriptional polymerase chain reaction（RTPCR）. Results Compared with RSR group, patients with CAF showed increased MMP-9 mRNA and protein expression（P〈 0.01） and decreased TIMP-1 mRNA and protein expression in the atrium（P 〈 0. 01）, but such changes were not observed in patients with PAF. The expression of MMP-1 at both the mRNA and protein levels showed no significant differences between the 3 groups. In CAF patients, MMP-9 mRNA and protein expressions in the left atrium was positively, but TIMP-1 expression was inversely correlated with the left atrium dimension and AF du ration（P 〈 0.01）, and a significant inverse correlation was indicated between MMP-9 and TIMP-1 expression at both the mRNA and protein levels. Conclusions MMP-9 expression is upregulated and TIMP-1 is downregulatcd in the left atrium of the RHD patients with AF. Disturbed balance between MMP-9 and TIMP-1 may promote the structural and functional changes of the atria and is associated with the occurrence and persistence of AF.