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目的探讨家兔慢性心力衰竭时心肌肌质网钙ATP酶(SERCA2)表达和功能的改变及血管紧张素Ⅱ受体拮抗剂缬沙坦长期干预的意义。方法 27只家兔随机分为3组,假手术组、心力衰竭组和缬沙坦组各9只。通过超容量负荷联合压力负荷建立家兔心力衰竭模型,于术后7周观察左心室结构、血流动力学的变化及SERCA2的表达和功能的改变。结果与假手术组比较,心力衰竭组左心室质量指数[(1.32±0.06)vs(3.61±0.09)g/kg]、左心室舒张末压[(-0.50±1.05)vs(23.00±2.37)mmHg)]显著升高(P<0.05),左心室短轴缩短率[(37.83±3.58)%vs(17.38±3.13)%]及左室射血分数[(72±5)%vs(38±6)%]明显降低(P<0.05);与心力衰竭组比较,缬沙坦组左心室质量指数和左心室舒张末压显著降低[(2.07±0.14)g/kg;(2.17±0.72)mmHg;P<0.05];左心室短轴缩短率及左室射血分数明显升高[(33.8±2.9)%;(65±4)%;P<0.05]。心力衰竭组SERCA2的表达[(0.69±0.04)vs(1.02±0.02)]和功能[(54.4±7.9)%vs(95.5±2.1)%]显著低于假手术组(P<0.05)。缬沙坦组SERCA2的表达和功能显著高于心力衰竭组[(0.91±0.02);(81.7±4.9)%;P<0.05]。结论缬沙坦长期干预,能够改善心力衰竭心脏舒缩功能,可能与增加SERCA2的表达和提高其功能有关。
Objective To investigate the changes of the expression and function of cardiac sarcoplasmic reticulum calcium ATPase (SERCA2) and the long-term intervention of angiotensin Ⅱ receptor antagonist valsartan in rabbits with chronic heart failure. Methods Twenty-seven rabbits were randomly divided into 3 groups: sham operation group, heart failure group and valsartan group. Rabbits with heart failure model were established by combined stress load and hypervolemic load. Changes of left ventricular structure, hemodynamics and SERCA2 expression and function were observed at 7 weeks after operation. Results Compared with the sham operation group, the left ventricular mass index [(1.32 ± 0.06) vs (3.61 ± 0.09) g / kg], left ventricular end diastolic pressure (-0.50 ± 1.05) vs (23.00 ± 2.37) mmHg ) Was significantly increased (P <0.05), shortening rate of left ventricular short axis [(37.83 ± 3.58)% vs (17.38 ± 3.13)%] and left ventricular ejection fraction (72 ± 5% vs 38 ± 6 )%] Significantly decreased (P <0.05). Compared with heart failure group, the left ventricular mass index and left ventricular end-diastolic pressure were significantly decreased in valsartan group [(2.07 ± 0.14) g / kg and (2.17 ± 0.72) P <0.05]. Left ventricular short axis shortening rate and left ventricular ejection fraction were significantly increased [(33.8 ± 2.9)%; (65 ± 4)%; P <0.05]. SERCA2 expression in heart failure group was significantly lower than that in sham operation group [(0.69 ± 0.04) vs (1.02 ± 0.02)] and functional [(54.4 ± 7.9)% vs (95.5 ± 2.1)%] groups. The expression and function of SERCA2 in valsartan group were significantly higher than those in heart failure group [(0.91 ± 0.02); (81.7 ± 4.9)%; P <0.05]. Conclusion Long-term intervention with valsartan can improve the cardiac systolic and diastolic function in heart failure, which may be related to increasing the expression of SERCA2 and enhancing its function.