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目的观察阿托伐他汀对压力负荷增高所致左心室肥厚(LVH)和心肌肌浆网钙泵(SERCA)活力的影响。方法雄性SD大鼠50只随机分为假手术组、腹主动脉缩窄(AAC)组、阿托伐他汀10mg/(kg·d)(Ato10mg)、阿托伐他汀30mg/(kg·d)(Ato30mg)和氨氯地平5mg/(kg·d)组,每组10只。采用腹主动脉缩窄术建立LVH动物模型,灌胃法给药4周。鼠尾容积法测量收缩压,计算左心室质量指数(LVMI),即左心室质量/体质量(LVM/BM);HE染色检测心肌细胞平均直径;无极磷酸根法测定SERCA活力;双波长荧光分光光度计检测心肌细胞内Ca2+浓度。结果与假手术组相比,AAC组收缩压、LVMI、心肌细胞平均直径、细胞内Ca2+浓度均显著升高,心肌SERCA活力(4.0±0.6)比假手术组(6.4±0.8)μmol/(mgpro.h)明显降低(均P<0.05)。与AAC组比较,阿托伐他汀30mg组及氨氯地平组均能降低大鼠收缩压、LVMI、心肌细胞平均直径和细胞内Ca2+浓度,同时能明显提高心肌SERCA活力[Ato30mg组(4.9±0.4),氨氯地平组(4.8±0.5)比AAC组(4.0±0.6)μmol/(mgpro·h),均P<0.05]。结论阿托伐他汀改善腹主动脉缩窄高血压大鼠LVH可能与增加SERCA活力,降低压力负荷诱导的肥厚心肌细胞中Ca2+浓度有关。
Objective To observe the effect of atorvastatin on left ventricular hypertrophy (LVH) and cardiac sarcoplasmic reticulum calcium pump (SERCA) activity induced by increased pressure overload. Methods 50 male SD rats were randomly divided into sham operation group, AAC group, atorvastatin 10 mg / (kg · d) (Ato10 mg) and atorvastatin 30 mg / (kg · d) (Ato30mg) and amlodipine 5mg / (kg · d) group, 10 in each group. LVH animal model was established by abdominal aortic constriction, and administered by gavage for 4 weeks. The systolic pressure was measured by tail volume method and the left ventricular mass index (LVMI) was calculated. The left ventricular mass / body mass (LVM / BM) was calculated. The mean diameter of cardiomyocytes was measured by HE staining. The SERCA activity was measured by non-polar phosphate assay. Photometric detection of intracellular Ca2 + concentration. Results Compared with the sham operation group, systolic blood pressure, LVMI, mean diameter of cardiomyocytes and intracellular Ca2 + concentration in AAC group were significantly higher than those in sham operation group (4.0 ± 0.6 vs 6.4 ± 0.8 μmol / (mgpro h) decreased significantly (all P <0.05). Compared with AAC group, both atorvastatin 30mg and amlodipine could reduce systolic blood pressure, LVMI, mean diameter of cardiomyocytes and intracellular Ca2 + concentration at the same time, and significantly increase myocardial SERCA activity [Ato30mg (4.9 ± 0.4 ), Amlodipine group (4.8 ± 0.5) than AAC group (4.0 ± 0.6) μmol / (mgpro · h), all P <0.05]. Conclusion Atorvastatin ameliorates LVH in hypertensive rats with abdominal aorta and may be related to increasing SERCA activity and decreasing Ca2 + concentration in hypertrophic cardiomyocytes induced by pressure overload.