心房肌基质金属蛋白酶-9和组织金属蛋白酶抑制因子-1表达改变对房颤心房重构机制的研究

Effects of matrix metalloproteinase-9 and t issue inhibitor-1 of metalloproteinase expression on atrial structural remodeli ng during chronic atrial fibrillation

目的探讨心房肌基质金属蛋白酶-9(MMP-9)和组织金属蛋白酶抑制因子-1(TIMP-1)表达水平的改变与慢性房颤心房结构重构的相关关系.方法选取进行人工瓣膜置换术的风湿性心脏病房颤24例为研究组,风湿性心脏病窦性心律12例为对照组.上述患者术前均进行经胸超声心动图检查,留取相关资料.于手术时取左心耳心肌标本,采用RT-PCR方法检测心房肌中本研究检测慢性房颤患者心房肌中MMP-9和TIMP-1的mRNA水平,采用免疫组织化学方法对MMP-9和TIMP-1蛋白质表达半定量分析.结果与对照组比较,风心房颤组左心房内径和右心房内径均显著扩大(P＜0.05～0.001),心肌中MMP-9 mRNA表达水平较对照组升高30.9%(P＜0.05);TIMP-1mRNA水平较对照组下调33.3%(P＜0.05);左心耳心肌组织中MMP-9蛋白质水平增高100%(P＜0.001),TIMP-1蛋白质水平减少36%(P＜0.01).左心耳心肌组织MMP-9 mRNA水平与房颤持续时间、左心房内径呈显著正相关(P＜0.05～0.001).结论房颤时心房肌组织MMP-9/TIMP-1系统相互间的作用失衡对心房壁变薄、心房扩大和几何形状改变具有重要作用,其机制是细胞外基质过度降解.

Objective To investigate the matrix metalloproteinase-9 (MMP-9) and tissue in hibitor-1 of metalloproteinase (TIMP-1) mRNA and protein expression in chronic fibrillating human atria and to evaluate the influence of MMP-9 and TIMP-1 ex pression on the progress of atrial structural remodeling.Methods Twenty-four patients with chronic atrial fibrillation (AF) and 12 pa tients with sinus rhythm as control group underwent transthoracic echocardiograp hy and left atrial appendage (LAA) tissue samples were obtained from these patie nts during mitral/aortic valve replacement operation. MMP-9 and TIMP-1 protei n expressions were detected by immunohistochemistry and their mRNA expressions w ere determined by reverse transcription polymerase chain reaction (RT-PCR).Results The left atrial and right atrial diameters increased significantly in the fibrillation group in comparison with the control group (57±6 vs 45±7,62 ±10 vs 51±17, P<0.05～0.001) The expressions of MMP-9 mRNA and protei n in the LAA tissue of the AF group is upregulated (0.70±0.12 vs 0.53±0.2 2,and 2.25±0.73 vs 1.12±0.58,P<0.05 ～0.001) and the expressions o f TIMP-1 mRNA and protein were downregulated significantly ( 0.20±0.07 vs 0 .31±0.15,and 1.12±0.48 vs 1.75±0.46, P<0.05～0.01). The MMP- 9 mRNA level was positively correlated with AF duration and the left atrial diam eter (P<0.05～0.001). Conclusion There is a selective downregulation of TIMP-1 expression along with the upregulation of MMP-9 in AF, which indicates that the disturbance expressio n of MMP/TIMP system may promote the process of atrial structural remodeling. E nhanced MMP-9 activity may be a molecular mechanism contributing to the dilatio n of fibrillating human atria.