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目的:观察辛伐他汀对慢性心力衰竭(心衰)兔心肌重构及心功能的影响,对心肌细胞中糖原合成激酶3β(GSK3β)活性、蛋白表达及β-连环蛋白(β-catenin)表达的影响。方法:24只新西兰白兔分为4组,每组6只。假手术组:为健康对照。其余兔行主动脉瓣反流及腹主动脉缩窄术,建立慢性心衰模型后,分为心衰对照组:术后不给药;早干预组:术后第2天给予辛伐他汀5 mg/(d.kg),连续8周;晚干预组:术后第4周给予辛伐他汀5 mg/(d.kg),连续4周。术后8周观察结束时行左心导管检查,记录左心室舒张末压,处死后称体重、心脏重量、左心室重量,计算心脏质量指数(心脏重量/体重)、左心室质量指数(左心室重量/体重)。West-ern-blotting分析心肌细胞浆GSK3β、细胞核β-catenin表达。免疫沉淀分析GSK3β活性。结果:术后8周时,心衰对照组左心室舒张末压、心脏重量、左心室重量、心脏质量指数及左心室质量指数均显著高于假手术组(P均<0.01);术后8周,早干预组心脏重量、左心室重量、心脏质量指数及左心室质量指数均显著低于心衰对照组(P<0.05～0.01);晚干预组心脏重量、左心室重量、心脏质量指数均显著低于心衰对照组(P<0.05～0.01)。术后8周,早干预组及晚干预组左心室舒张末压均显著低于心衰对照组(P均<0.05)。心衰对照组心肌胞浆中GSK3β活性较假手术组显著降低(P<0.01),而心肌细胞核β-catenin表达显著增加(P<0.01),差异均有统计学意义。早干预组及晚干预组GSK3β活性与心衰对照组比较均显著增加(P均<0.01),而心肌细胞核β-catenin表达均显著降低(P均<0.01)。结论:辛伐他汀治疗有效抑制心力衰竭兔心肌重构、改善心功能;其作用与增加GSK3β活性、抑制心肌细胞核β-catenin表达有关。
AIM: To observe the effect of simvastatin on cardiac remodeling and cardiac function in rabbits with chronic heart failure (CHF), the effects of simvastatin on the activity of GSK3β, the expression of β-catenin, The impact of expression. Methods: 24 New Zealand white rabbits were divided into 4 groups, 6 in each group. Sham operation group: for healthy control. The other rabbits underwent aortic regurgitation and abdominal aortic constriction, the establishment of chronic heart failure model, divided into heart failure control group: no administration after surgery; early intervention group: the first 2 days after the administration of simvastatin 5 mg / (d.kg) for 8 weeks; late intervention group: simvastatin 5 mg / (d.kg) 4 weeks after the operation for 4 weeks. Left ventricular end-diastolic pressure was recorded at the end of 8 weeks after operation. Left ventricular end-diastolic pressure was recorded and weight, cardiac weight and left ventricular weight were calculated at the end of the operation. Heart mass index (heart weight / body weight), left ventricular mass index Weight / weight). West-ern-blotting analysis of cardiac myocyte GSK3β, nuclear β-catenin expression. Immunoprecipitation analysis of GSK3β activity. Results: Left ventricular end-diastolic pressure, heart weight, left ventricular mass, cardiac mass index and left ventricular mass index were significantly higher in the heart failure control group than in the sham operation group at 8 weeks after operation (P <0.01) The heart weight, left ventricular mass, cardiac mass index and left ventricular mass index in the early intervention group and the early intervention group were significantly lower than those in the control group (P <0.05-0.01). The cardiac weight, left ventricular weight and heart mass index Significantly lower than the control group (P <0.05 ~ 0.01). After 8 weeks, the left ventricular end-diastolic pressure in early intervention group and late intervention group were significantly lower than those in the control group (all P <0.05). The activity of GSK3β in cardiomyocytes in heart failure group was significantly lower than that in sham operation group (P <0.01), while the expression of β-catenin in cardiomyocytes was significantly increased (P <0.01). The difference was statistically significant. GSK3βactivity in early intervention group and late intervention group were significantly increased compared with the control group (all P <0.01), while the expression of β-catenin in myocardial cells was significantly decreased (all P <0.01). Conclusion: Simvastatin can effectively inhibit myocardial remodeling and improve cardiac function in rabbits with heart failure. Its effect is related to increasing GSK3β activity and inhibiting β-catenin expression in myocardial cells.