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目的研究辛伐他汀对压力超负荷大鼠心肌核转录因子κB(NF-κB)活化的影响及其与心肌肥厚之间的关系,探讨辛伐他汀改善压力超负荷大鼠心肌肥厚的机制。方法大鼠32只分为4组:心肌肥厚组:仅缩窄升主动脉;吡咯烷二硫基甲酸盐(PDTC)组:缩窄升主动脉,并腹腔注射PDTC80mg/(kg.d);辛伐他汀组:缩窄升主动脉,并用辛伐他汀40mg/(kg.d)进行灌胃;假手术组:开胸,不缩窄升主动脉。2周后应用超声心动图评价心脏功能,计算左室质量/体质量的比值,Westernblot检测心肌匀浆中磷酸化NF-κB抑制因子α(p-IκB-α)与NF-κB抑制因子α(IκB-α)蛋白质的表达,ELISA检测心肌匀浆中NF-κBp65的水平。结果与假手术组比较,缩窄升主动脉引起大鼠左室质量/体质量的比值及舒张末期左室内径(LVEDD)显著增加,心肌匀浆中p-IκB-α显著增加,IκB-α显著减少,同时伴随心肌匀浆中NF-κBp65的水平增加;PDTC与辛伐他汀均能抑制缩窄升主动脉引起大鼠左室质量/体质量的比值及LVEDD显著增加,同时其能抑制心肌匀浆中p-IκB-α显著增加、IκB-α显著减少及NF-κBp65水平的增加。结论NF-κB的活化可能参与了缩窄升主动脉引起压力超负荷所致大鼠心肌肥厚,辛伐他汀可能通过抑制压力超负荷大鼠心肌NF-κB的活化发挥抑制心肌肥厚的作用。
Objective To investigate the effect of simvastatin on the activation of nuclear factor kappa B (NF-κB) in cardiac muscle of hypertensive rats and its relationship with cardiac hypertrophy, and to explore the mechanism of simvastatin in improving myocardial hypertrophy induced by pressure overload in rats. Methods Thirty-two rats were divided into 4 groups: cardiac hypertrophy group: only the ascending aorta was narrowed; pyrrolidine dithioformate (PDTC) group: the ascending aorta was astigmatism and PDTC80mg / (kg.d) ; Simvastatin group: ascending aorta narrowed, and simvastatin 40mg / (kg.d) for gavage; sham operation group: thoracotomy, not narrowing the ascending aorta. The heart function was evaluated by echocardiography after 2 weeks. The ratio of left ventricular mass to body mass was calculated. Western blot was used to detect the expression of phosphorylated NF-κB inhibitor α (p-IκB-α) and NF-κB inhibitor α IκB-α) protein was detected by enzyme-linked immunosorbent assay. The level of NF-κB p65 in myocardial homogenate was detected by ELISA. Results Compared with the sham-operation group, the ratio of left ventricular mass to body mass and end-diastolic left ventricular diameter (LVEDD) in ascending aorta were significantly increased, the level of p-IκB-α in myocardial homogenate was significantly increased, While the level of NF-κBp65 was increased in myocardial homogenate. Both PDTC and simvastatin could inhibit the ratio of left ventricular mass / body mass and LVEDD of ascending aorta in rats, and at the same time, it could inhibit myocardium In the homogenate, p-IκB-α significantly increased, IκB-α significantly reduced and NF-κB p65 levels increased. Conclusion Activation of NF-κB may be involved in myocardial hypertrophy induced by pressure overload in ascending aorta of rats. Simvastatin may inhibit cardiac hypertrophy by inhibiting the activation of NF-κB in pressure overload rats.