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目的研究辛伐他汀对心肌梗死(MI)大鼠心肌TLR4及其下游炎性因子TNFα-与IL-6表达的影响及其与心室重构的关系,探讨辛伐他汀改善MI心室重构的机制。方法30只大鼠分为3组,每组10只:1)MI组:仅结扎左冠状动脉前降支(LAD);2)辛伐他汀组:结扎LAD,并用辛伐他汀40 mg/(kg.d)进行灌胃4周;3)假手术组:开胸,但不结扎LAD。应用超声心动图检测左室形态与功能;RT-PCR与Western blot分别检测各组心肌中TLR4 mRNA与蛋白质表达;ELISA检测各组心肌匀浆中炎症因子TNF-α与IL-6的水平。将TLR4蛋白质分别与左室舒张末期内径(LVEDd)、TNF-α及IL-6水平进行相关分析。结果超声心动图显示:MI组与假手术组比较,LVEDd明显增加,射血分数(EF)和短轴缩短率(FS)明显减少;与MI组比较,辛伐他汀能够明显抑制MI后左室扩张,改善左室功能。与假手术组比较,MI组心肌组织中TLR4 mRNA与蛋白质、炎症因子TNF-α与IL-6的水平均明显增加;辛伐他汀能够明显抑制MI后心肌组织中TLR4 mRNA与蛋白质、炎症因子TNF-α与IL-6的表达。相关性分析表明:在MI组与辛伐他汀组,TLR4蛋白质分别与LVEDd、TNF-α及IL-6水平呈正相关。结论辛伐他汀改善MI大鼠心室重构的作用可能与其抑制MI心肌TLR4及其下游炎症因子TNF-α与IL-6的表达有关。
Objective To investigate the effect of simvastatin on the expression of TLR4 and its downstream inflammatory cytokines TNFα and IL-6 in myocardial infarction (MI) rats and its relationship with ventricular remodeling and to explore the mechanism of simvastatin in improving myocardial remodeling . Methods Thirty rats were randomly divided into three groups (n = 10): 1) MI group: ligated only left anterior descending artery (LAD); 2) simvastatin group: LAD was ligated and simvastatin 40 mg / kg.d) for 4 weeks; 3) sham operation group: thoracotomy, but not ligation of LAD. The morphology and function of left ventricle were detected by echocardiography. The expressions of TLR4 mRNA and protein were detected by RT-PCR and Western blot respectively. The levels of TNF-α and IL-6 in myocardial homogenate were measured by ELISA. TLR4 protein and left ventricular end-diastolic diameter (LVEDd), TNF-α and IL-6 levels were analyzed. Results Echocardiography showed that the LVEDd was significantly increased and the ejection fraction (EF) and short axis shortening (FS) were significantly decreased in the MI group compared with the sham operation group. Compared with the MI group, Simvastatin significantly inhibited left ventricular Expansion, improve left ventricular function. Compared with the sham group, the levels of TLR4 mRNA and protein, inflammatory cytokines TNF-α and IL-6 in myocardium of MI group were significantly increased; simvastatin could significantly inhibit the expression of TLR4 mRNA and protein, inflammatory factor TNF -α and IL-6 expression. Correlation analysis showed that there was a positive correlation between TLR4 protein and LVEDd, TNF-α and IL-6 levels in MI group and simvastatin group. Conclusion The effect of simvastatin on ventricular remodeling in MI rats may be related to the inhibition of the expression of TLR4 and its downstream inflammatory cytokines TNF-α and IL-6 in MI myocardium.