RhoA经基质金属蛋白酶-3、-9通路介导心力衰竭大鼠心肌重塑及心功能恶化

目的:探讨RhoA、Rho激酶、基质金属蛋白酶家族(MMPs)MMP-3、MMP-9表达与心肌重塑及心功能损害的关系。方法:建立假手术组及心力衰竭大鼠(造模12周及20周)模型。应用Nikon 4多导生理记录仪检测血液动力学指标以评价心功能情况,心肌肥厚指数及H-E染色评价心肌重塑情况,并采用RT-PCR方法检测各组大鼠心肌组织RhoA、Rho激酶及MMP-3、MMP-9基因表达。结果:造模20周、造模12周心力衰竭组大鼠与假手术组大鼠对比,随心肌重塑加重、心功能恶化,RhoA、Rho激酶及MMP-3、MMP-9基因表达显著增加,且直线相关分析结果显示RhoA基因表达与Rho激酶、MMP-3、MMP-9基因表达呈正相关趋势。结论:RhoA可能通过刺激MMP-3、MMP-9的表达引起细胞外基质结构发生改变,引起心肌重塑和心功能恶化。

RhoA regulates the myocardial remodeling and functional deterioration through matrix metalloproteinase-3 and 9

Objective: To study the relationship between the expressions of RhoA, Rho kinase and matrix metalloproteinase-3, 9 and myocardial remodeling and functional deterioration in heart failure model rats. Methods: 20 heart failure rats and 10 age-matched sham operation rats were prepared for this experiment. We detected the gene expressions of RhoA, Rho kianase and MMP-3, 9 on myocardial tissue in the heart failure rats and in the sham operation rats. Cardiac function perameters and H-E staining were measured. Results: With myocardial remodeling and functional deterioration, the gene expressions of RhoA and RhoA kinase were increased significantly compared with those in sham group, which were positive correlated with the expressions of MMP-3 and MMP-9 in mRNA level.Conclusion: It suggests that alterations of RhoA and Rho kinase may contribute to myocardial remodeling and lead to the development and progression of congestive heart failure by stimulating the expressions of MMP-3, 9. These changes may induce a direct effect on the progression and deterioration of cardiac muscle remodeling and heart failure.