肿瘤坏死因子α和基质金属蛋白酶家族与左室重构的关系

Tumor necrosis factor alpha and myocardial matrix metalloproteinases in left ventricular remodeling

目的 探讨肿瘤坏死因子 (TNF)α与基质金属蛋白酶家族 (MMPs)MMP 2、3、9与心肌重构、心功能损害的关系。方法 采用双抗体夹心ELISA法测定心力衰竭 (心衰 )患者TNFα血浓度 ,Westernblot法对 31例风湿性心脏病 (RHD)心衰患者及 8例健康人心室肌组织中MMP 2、3、9蛋白表达含量进行半定量分析 ;RHD患者术前心功能指标采用超声心动图检查。结果 心衰患者TNFα血浓度随心衰加重而增高 (P <0 0 5或 <0 0 1) ,心肌组织MMP 2、3、9蛋白表达随心衰程度加重而增加 (P <0 0 5或程 <0 0 1) ,TNFα血浓度与心肌组织MMP 2、3、9蛋白表达存在明显的正相关关系 (P <0 0 1或 <0 0 0 1)。结论 TNFα可能通过刺激MMPs的表达 ,引起细胞外基质结构发生改变 ,加重心衰时的左室重构 。

Objective The cytokine tumor necrosis factor (TNF) alpha has been causally linked to left ventricular (LV) remodeling, but the molecular basis for this effect is unknown. It is essential to study the changes of plasma levels of TNF alpha and matrix metalloproteinase-2,3,9 (MMP-2,3,9) expressions in myocardium during congestive heart failure(CHF).Methods Plasma levels of TNF alpha were measured with enzyme-linked immunoassay in CHF patients of various degrees and in healthy controls. Using Western blotting assay, we detected the protein expressions of MMP-2,3,9 on myocardial tissue in CHF patients and in healthy controls. Cardiac function parameters were measured with echocardiographic studies. Results Plasma levels of TNF alpha increased significantly in patients with CHF ( P <0.05 or <0.01). The protein expressions of MMP-2,3,9 were significantly higher in patients with CHF than in controls ( P <0.05 or <0.01). The higher the degree of CHF, the greater the numbers of expressions. No changes of MMP-2 could be found between the controls and CHF patients of NYHA Ⅱ. There was a positive correlation between plasma levels of TNF alpha and the protein expressions of MMP-2,3,9 ( P <0.01 or <0.001).Conclusions It is suggested that alterations of TNF alpha may stimulate the expressions of MMPs, contribute to myocardial remodeling and lead to the development and progression of congestive heart failure. These changes may induce a direct effect on the progression and deterioration of heart failure.