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目的:建立压力负荷性心衰大鼠模型,观察白藜芦醇对心肌收缩功能的保护作用及对心肌钙调控蛋白表达的影响。方法:以腹主动脉缩窄法建立大鼠压力过负荷心肌肥大模型,术后4周给予白藜芦醇[4 mg/(kg·d)]治疗4周和6周,用IE 33彩超仪无创测量左室室壁厚度以及射血功能相关指标;实时定量PCR法检测左心室组织匀浆中CaMKⅡ、PLB、NCX_1、SERCA_2、RYR_2的mRNA的表达。结果:术后4周,与假手术组相比,腹主动脉缩窄大鼠左室室壁厚度、射血分数(EF)及收缩系数(FS)明显增高(P<0.05)。术后8周和10周,即药物干预后4周和6周,与假手术组相比,单纯手术组EF及FS明显降低(P<0.05);白藜芦醇干预组EF和FS较单纯手术组明显升高(P<0.05),且与假手术组比无显著差别。另外,与假手术组比较,单纯手术组CaMKⅡ、PLB、NCX_1的mRNA表达均明显增高(P<0.05),而SERCA_2、RYR_2的mRNA表迭明显降低(P<0.05);经白藜芦醇干预4周和六周后,CaMKⅡ、PLB、NCX_1的mRNA表达明显下调(P<0.05);SERCA_2、RYR_2的mRNA表达则明显回升(P<0.05)。结论:白藜芦醇可显著改善压力负荷所致的心脏收缩功能损害,阻止心脏向失代偿阶段演变,其作用可能与调控心肌细胞中多种钙调节蛋白表达有关。
OBJECTIVE: To establish a rat model of stress-induced heart failure and observe the protective effects of resveratrol on myocardial contractile function and its effect on the expression of cardiac calcium-regulated protein. Methods: A rat model of myocardial hypertrophy induced by pressure overload was established by abdominal aorta stenosis. Resveratrol [4 mg / (kg · d)] was given for 4 weeks and 6 weeks after operation, Non-invasive measurement of left ventricular wall thickness and ejection function related indicators; real-time quantitative PCR method to detect left ventricular tissue homogenate CaMKⅡ, PLB, NCX_1, SERCA_2, RYR_2 mRNA expression. Results: Left ventricular wall thickness, ejection fraction (EF) and contractile index (FS) were significantly increased in abdominal aorta constriction rats at 4 weeks after operation (P <0.05). Compared with the sham operation group, the EF and FS of the operation group were significantly lower at 8 and 10 weeks after operation (P <0.05). The EF and FS of the resveratrol group were lower than those of the sham operation group The operation group was significantly higher (P <0.05), and no significant difference with the sham operation group. In addition, mRNA expression of CaMKⅡ, PLB and NCX_1 were significantly increased (P <0.05), while SERCA_2 and RYR_2 mRNA expressions were significantly decreased (P <0.05) After 4 and 6 weeks, the mRNA expressions of CaMKⅡ, PLB and NCX_1 were significantly down-regulated (P <0.05). The mRNA expressions of SERCA_2 and RYR_2 were significantly increased (P <0.05). CONCLUSION: Resveratrol can significantly improve cardiac contractile dysfunction caused by pressure overload and prevent the heart from evolving into decompensation stage, which may be related to the regulation of many calcium regulatory proteins in cardiomyocytes.