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目的探讨家兔慢性心力衰竭时心肌肌浆网钙泵(SERCA2)表达和功能的改变及辛伐他汀长期干预的意义。方法21只家兔随机分为3组:假手术组(n=7)、心力衰竭组(n=7)和辛伐他汀组[n=7,10mg/(kg.d),主动脉关闭不全后第2天给药],通过超容量负荷联合压力负荷建立家兔心力衰竭模型,术后7周用心脏超声测定左室短轴缩短率(LVFS)及左室射血分数(LVEF),心导管术测定左室收缩末压(LVESP)、左室舒张末压(LVEDP),称量左室质量,计算左室质量指数(LVMI);用半定量RT-PCR及免疫印迹法检测SERCA2的表达,检测SERCA2活性及肌浆网摄钙能力。结果与假手术组比较,心力衰竭组家兔LVMI[(3.61±0.09)比(1.32±0.06)g/kg]、LVEDP明显升高,LVFS及LVEF[(38.5±5.1)%比(71.9±4.6)%]明显降低(均P<0.05);辛伐他汀显著降低心力衰竭家兔的LVMI[(2.17±0.13)g/kg]、LVEDP,明显升高LVFS、LVEF[(62.2±3.3)%,均P<0.05]。心力衰竭组SERCA2的表达和活性显著低于假手术组[mRNA(0.70±0.04)比(1.06±0.16),蛋白(0.69±0.04)比(1.02±0.02),活性(8.32±0.15)比(15.01±1.00)μmolPi/(mgpro.h),均P<0.05];辛伐他汀显著提高心力衰竭家兔SERCA2的表达和活性[mRNA,辛伐他汀组(0.86±0.02)比心力衰竭组(0.70±0.04);蛋白,辛伐他汀组(0.87±0.03)比心力衰竭组(0.69±0.04);活性,辛伐他汀组(11.81±0.63)比心力衰竭组(8.32±0.15)μmolPi/(mgpro.h),均P<0.05]。心力衰竭组肌浆网摄钙能力较假手术组明显降低,辛伐他汀提高心力衰竭家兔的肌浆网摄钙能力。结论辛伐他汀长期干预心力衰竭能够改善心脏舒缩功能,可能与其增加SERCA2的表达和功能有关。
Objective To investigate the expression and function of cardiac sarcoplasmic reticulum calcium pump (SERCA2) in rabbits with chronic heart failure and the significance of long-term intervention of simvastatin. Methods Twenty-one rabbits were randomly divided into three groups: sham operation group (n = 7), heart failure group (n = 7) and simvastatin group [n = 7,10 mg / (kg · d) After the second day of administration], rabbits with heart failure model were established by super-capacity load combined with pressure load, left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) The left ventricular end systolic pressure (LVESP) and left ventricular end-diastolic pressure (LVEDP) were measured by catheterization, the left ventricular mass was measured and the left ventricular mass index (LVMI) was calculated. The expression of SERCA2 was detected by semi-quantitative RT-PCR and Western blotting , Testing SERCA2 activity and sarcoplasmic reticulum calcium uptake capacity. Results Compared with the sham operation group, the LVEDP was significantly higher in the heart failure group than in the LVMI group (3.61 ± 0.09 vs 1.32 ± 0.06 g / kg, LVEDP [(38.5 ± 5.1)% vs (71.9 ± 4.6) ) Were significantly lower than those in control group (all P <0.05); Simvastatin significantly reduced LVMI [(2.17 ± 0.13) g / kg], LVEDP, LVFS and LVEF [(62.2 ± 3.3) All P <0.05]. The expression and activity of SERCA2 in heart failure group were significantly lower than those in sham group [mRNA (0.70 ± 0.04) vs (1.06 ± 0.16), protein (0.69 ± 0.04) vs (1.02 ± 0.02) ± 1.00) μmolPi / (mgpro.h), all P <0.05]. Simvastatin significantly increased SERCA2 expression and activity in heart failure rabbits (0.86 ± 0.02 vs. 0.70 ± 0.04), simvastatin group (0.87 ± 0.03) and heart failure group (0.69 ± 0.04); activity, simvastatin group (11.81 ± 0.63) and heart failure group (8.32 ± 0.15) μmolPi / ), All P <0.05]. Cardiac sarcoplasmic reticulum calcium intake in heart failure group was significantly lower than that in sham operation group, and simvastatin increased sarcoplasmic reticulum calcium uptake in heart failure rabbits. Conclusion Long-term intervention of simvastatin can improve cardiac systolic and diastolic function, which may be related to the increase of SERCA2 expression and function.