心房肌基质金属蛋白酶-2和组织金属蛋白酶抑制因子-2的表达改变对风湿性心脏病二尖瓣狭窄合并房颤患者心房结构重构机制的研究

A research on the effects of matrix metalloproteinase-2 and tissue inhibitor-2 of metalloproteinase expression on atrial structural remodeling in patients with atrial fibrillation caused by rheumatic heart disease

目的探讨基质金属蛋白酶-2(MMP-2)和组织金属蛋白酶抑制因子-2(TIMP-2)的基因表达水平变化与风湿性心脏病二尖瓣狭窄合并房颤患者心房结构重构的相关关系。方法选取进行二尖瓣置换术的风湿性心脏病二尖瓣狭窄合并房颤患者42例为房颤组;风湿性心瓣膜病窦性心律l8例为对照组。上述患者术前均行经胸超声心动图检查及留取相关临床资料。于手术时取左心耳心肌标本,采用Masson三色染色法检测心房肌组织纤维化程度;RT-PCR方法检测心房肌组织MMP-2和TIMP-2的mRNA水平。结果(1)房颤组患者心房肌组织纤维化比例较对照组显著升高(P<0.01),心肌组织纤维化程度与左房内径(r=0.788,P<0.001)呈显著正相关,与二尖瓣口面积(r=-0.886,P<0.05)呈负相关;(2)与对照组比较,房颤组患者心房肌组织MMP-2mRNA表达量增高(P<0.05);TIMP-2mRNA表达量降低(P<0.05)。(3)MMP-2和TIMP-2mRNA表达水平之间呈显著负相关(rp=-0.766,P<0.001)。MMP-2mR-NA表达水平与左心耳心肌组织纤维化程度(rp=0.919,P<0.001)呈显著正相关;TIMP-2mRNA表达水平与左心耳心肌组织纤维化程度(rp=-0.883,P<0.001)呈显著负相关。结论心房组织MMP-2和TIMP-2的基因表达改变,尤其是MMP-2/TIMP-2表达的失衡,是风湿性心脏病二尖瓣狭窄时心房扩大及房颤发生与维持的重要机制之一。

Objective To investigate the matrix metalloproteinase-2 （MMP-2） and tissue inhibitor-2 of metalloproteinase （TIMP-2） mRNA expression in patients with atrial fibrillation caused by rheumatic heart disease and to evaluate the influence of MMP-2 and TIMP-2 expression on the progress of atrial structural remodeling. Methods 42 patients with chronic atrial fibrillation（AF） caused by mitral valve straitness of rheumatic heart disease were as experimental group, and 18 patients with sinus rhythm were as control group. Before operation, all of the above patients underwent transthoracic echocardiograph, and related clinical date were collected. Left atrial appendage （LAA） tissue samples were obtained from these patients during mitral valve replacement operation. Collagen fibers in left atrial appendage were observed by Masson trichrome stain. MMP-2 and TIMP-2 mRNA expressions were determined by reverse transcription polymerase chain reaction （RT-PCR）. Results （ 1 ） Compare with control group,the content of collagen fibers in LAA increased significantly in patients with AF（ P 〈0.01 ）. The content of collagen fibers in LAA was significantly correlated with left atrial dimension（ r = 0. 788, P 〈 0.001 ） and the aera of mitral valve （ r = - 0. 886, P 〈 0.05 ）. （2） Compared with control group,the expressions of MMP-2 mRNA（ P 〈 0.05 ） in the LAA tissue of the AF group was up-regulated significantly;the expressions of TIMP-2 mRNA （P 〈 0.05 ） in the LAA tissue of the AF group was down-regulated significantly. （3）The expressions of M MP-2 mRNA was signifi- cantly correlated with TIMP-2 mRNA （ rp = - 0. 766, P 〈 0. 001 ）. The MMP-2 was significantly correlated with the content of collagen fibers in LAA（ r, =0. 869 ,P 〈 0. 001 ）. The TIMP-2 was significantly correlated with the content of collagen fibem in LAA （ rp = - 0. 830, P 〈 0. 001 ）.Conclusion The selective down-regulation of TIMP-2 and up-regulation of MMP-2 gene expression in atrium,especially the unbalanced change of the MMP-2 and TIMP-2 gene expression ,could be one of the molecular mechanisms of atrial structural remodeling in patients with atrial fibrillation caused by rheumatic heart disease ,which correlates with the initiation and maintenance of AF.