主管单位:中华人民共和国
国家卫生健康委员会
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编辑部主任:吴翔宇
邮发代号:80-528
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英文作者:Wu Shaowei1 Liu Chengwei1 Xu Chengyi2
单位:1武汉亚洲心脏病医院心内科,武汉430000;2武汉亚洲心脏病医院心脏急危重症诊疗中心,武汉430000
英文单位:1Department of Cardiology Wuhan Asia Heart Hospital Wuhan 430000 China; 2Department of Cardiac Critical Care Center Wuhan Asia Heart Hospital Wuhan 430000 China
英文关键词:Heartfailure;Suixincapsules;Calciumregulatingprotein;Cardiacfunction
目的 探讨燧心胶囊对心力衰竭大鼠心功能及心肌组织钙调控蛋白肌浆网钙离子三磷酸腺苷酶2a(SERCA2a)、兰尼碱受体2(RyR2)、受磷蛋白水平的影响。方法 将30只清洁级SD大鼠完全随机分为对照组、假手术组、模型组、低剂量组及高剂量组,各6只。除对照组和假手术组大鼠外,其余各组大鼠均采用腹主动脉缩窄术建立慢性心力衰竭模型,对照组、假手术组和模型组大鼠给予0.9%氯化钠溶液灌胃,低、高剂量组大鼠将对应剂量燧心胶囊溶于2 ml 0.9%氯化钠溶液灌胃,连续给药12周后,脱臼处死大鼠。比较各组大鼠给药12周后心功能指标[左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、左心室射血分数(LVEF)],钙调控蛋白SERCA2a、RyR2、受磷蛋白水平和细胞凋亡蛋白半胱氨酸天冬氨酸蛋白酶3(Caspase-3)、Caspase-6水平变化,分析心功能与钙调控蛋白、细胞凋亡蛋白水平的相关性。结果 模型组大鼠的LVESD、LVEDD明显高于对照组和假手术组,LVEF明显低于对照组和假手术组,且低剂量组和高剂量组大鼠的LVESD、LVEDD明显低于模型组[(4.87±1.09)、(4.66±0.98)mm比(6.45±1.06)mm;(8.46±1.53)、(8.38±1.40)mm比(9.96±1.67)mm],LVEF明显高于模型组[(68.5±1.6)%、(67.8±4.1)%比(57.7±9.7)%](均P<0.05)。模型组大鼠的心肌钙调控蛋白SERCA2a、RyR2、受磷蛋白mRNA及蛋白表达水平均明显低于对照组和假手术组,且低剂量组和高剂量组明显高于模型组(均P<0.05)。模型组大鼠心肌组织细胞凋亡蛋白Caspase-3、Caspase-6表达水平明显高于对照组和假手术组,且低剂量组和高剂量组明显低于模型组[(0.32±0.06)、(0.29±0.04)比(0.39±0.09);(0.30±0.07)、(0.25±0.06)比(0.36±0.04)](均P<0.05)。心肌钙调控蛋白SERCA2a、RyR2及受磷蛋白蛋白表达水平均与LVEF呈正相关(r=0.571,P=0.001;r=0.793,P<0.001;r=0.584,P<0.001),细胞凋亡蛋白Caspase-3及Caspase-6蛋白表达水平均与LVEF呈负相关(r=-0.736,P<0.001;r=-0.674,P<0.001)。结论 燧心胶囊可有效改善心力衰竭大鼠的心功能,其治疗作用可能与调控大鼠心肌组织钙调控蛋白SERCA2a、RyR2及受磷蛋白和细胞凋亡蛋白水平有关。
Objective To investigate the effects of Suixin capsules on cardiac function and levels of myocardial calcium regulatory protein sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a), ryanodine receptor 2 (RyR2) and phospholamban (PLB) in rats with heart failure. Methods Thirty clean SD rats were randomly divided into control group, sham operation group, model group, low dose group and high dose group, with 6 rats in each group. Except for the control group and sham operation group, rats in other groups were treated with abdominal aortic coarctation to establish the rat model of chronic heart failure. The rats in the control group, sham operation group and model group were given 0.9% saline chloride solution intragastric administration. Rats in low and high dose groups were given matched doses Suixin capsules dissolving in 2 ml of 0.9% sodium chloride solution by intragastric administration. After 12 weeks of continuous administration, the rats were executed. The changes of cardiac function indexes [left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF)], the levels of calcium regulatory proteins SERCA2a, RyR2, PLB, apoptosis proteins Caspase-3 and Caspase-6 were compared. The correlation of cardiac function with the levels of calcium regulatory protein and apoptosis protein was analyzed. Results The LVESD and LVEDD of model group were significantly higher than those of control group and sham operation group, LVEF of model group was significantly lower than those of control group and sham operation group, LVESD and LVEDD of low dose group and high dose group were significantly lower than those of model group[(4.87±1.09),(4.66±0.98)mm vs (6.45±1.06)mm;(8.46±1.53),(8.38±1.40)mm vs (9.96±1.67)mm], and the LVEF was significantly higher than that of model group[(68.5±1.6)%,(67.8±4.1)% vs (57.7±9.7)%] (all P<0.05). The expression levels of myocardial calcium regulatory proteins SERCA2a, RyR2, PLB mRNA and protein of model group were significantly lower than those of control group and sham operation group, and those of low dose group and high dose group were significantly higher than those of model group (all P<0.05). The expression levels of apoptotic proteins Caspase-3 and Caspase-6 in myocardial tissue of model group were significantly higher than those of control group and sham operation group, and those of low dose group and high dose group were significantly lower than those of model group[(0.32±0.06),(0.29±0.04) vs (0.39±0.09);(0.30±0.07),(0.25±0.06) vs (0.36±0.04)](all P<0.05). The expression levels of cardiac calcium regulatory proteins SERCA2a, RyR2 and PLB were positively correlated with LVEF(r=0.571,P=0.001;r=0.793,P<0.001;r=0.584,P<0.001), and the expression levels of apoptotic proteins Caspase-3 and Caspase-6 were negatively correlated with LVEF(r=-0.736,P<0.001;r=-0.674,P<0.001). Conclusion Suixin sapsules can effectively improve the cardiac function in rats with heart failure, which may be related to its effect on the levels of SERCA2a, RyR2, PLB and apoptosis proteins in myocardial tissue of rats.
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