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、NCX1、SERCA2、RYR2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、NCX1的 mRNA 表达均明显增高(P〈0.05),而 SERCA2、RYR2的 mRNA 表达明显降低(P〈0.05);经白藜芦醇干预4周和六周后,CaMKⅡ、PLB、NCX1的 mRNA 表达明显下调(P〈0.05);SERCA2、RYR2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 observe the protection of resveratrol on cardiac contractile function and its regulation on the expression of Ca2+ hanlding proteins in rats with pressure overload. Methods Pressure-overload cardiac hypertrophy model was built by abdominal aortic constriction (AAC) in rats. 4 weeks after the operation, the rats were treated with resveratrol (4mg/ (kg·day) for 4 weeks and 6 weeks. IE 33 echocardiography was used to measure the thickness of walls and ejection functions of left ventricle(LV). The mRNA expression of Ca2+hanlding proteins including CaMK Ⅱ、PLB、NCX1、SERCA2、 RYR2 were detected with Real-time PCR assay. Results 4 weeks after the operation, the thickness of LV walls, ejection fraction (EF) and fractional shortening (FS) in AAC rats were significantly higher than those in sham group (P〈0.05). 8 and 10 weeks after operation, namely 4 and 6 weeks after treatment with resveratrol, EF and FS in AAC group were significantly reduced compared with sham rats (P〈0.05). However, EF and FS in rats treated with resveratrol were significantly higher than banded rats, and had no obvious difference compared with sham group (P〈0.05). Moreover, compare to sham rats, the mRNA expressions of CaMKⅡ、PLB、NCX1 in AAC group were remarkably higher, accompanied with decreased SERCA2、RYR2(P〈0.05). After 4 and 6-week treatment with resveratrol, the mRNA expressions of CaMKⅡ、PLB、NCX1 were down-regulated effectively, and SERCA2、RYR2 were distinctly elevated (P〈0.05). Conclusion Resveratrol ameliorated cardiac systolic dysfunction caused by pressure overload, and prevented the transitions of cardiac function from compensatory to decompensatory stage, which might work through controlling and regulating the expression of various Ca2+ handling proteins in myocardial cells.