The aim of this study was to investigate whether ellagic acid (EA) treatment can prevent changes in contractile function and Ca²⁺ regulation of cardiomyocytes in pathologic cardiac hypertrophy. Groups were assigned as Con group; an ISO group in which the rats received isoproterenol alone (5 mg/kg/day); and an ISO + EA group in which the rats received isoproterenol and EA (20 mg/kg/day) for 4 weeks. Subsequently, fractional shortening, intracellular Ca²⁺ signals, and L-type Ca²⁺ currents of isolated ventricular myocytes were recorded. Protein expression levels were also determined by the Western blotting method. The survival rate was increased, and the upregulated cardiac hypertrophy markers were significantly attenuated with the EA treatment. The fractional shortening and relaxation rate of myocytes was decreased in the ISO group, whereas EA significantly improved these changes. Ventricular myocytes of the ISO + EA rats displayed lower diastolic Ca²⁺ levels, higher Ca²⁺ transients, shorter Ca²⁺ decay, and higher L-type Ca²⁺ currents than those of ISO rats. Protein expression analyses indicated that the upregulated p-PLB and p-CaMKII expressions were restored by EA treatment, suggesting improved calcium handling in the ISO + EA rat heart. Moreover, ISO rats displayed significantly increased expression of p-22^phox and p47^phox subunits of NOX2 protein. Expression of the p22^phox subunit was reduced with EA administration, while the decrease in p47^phox did not reach a significant level. The increased ROS impairs Ca²⁺ homeostasis and contractile activity of cardiac myocytes, whereas chronic EA administration prevents Ca²⁺ dysregulation and functional abnormalities associated with pathological cardiac hypertrophy via the diminution of oxidative stress.

本研究的目的是探讨鞣花酸 (EA) 治疗是否可以预防病理性心脏肥大中心肌细胞收缩功能和 Ca ²⁺调节的变化。各组被指定为Con组； ISO 组，其中大鼠单独接受异丙肾上腺素（5 毫克/公斤/天）； ISO + EA 组，大鼠接受异丙肾上腺素和 EA（20 mg/kg/天）4 周。随后，记录离体心室肌细胞的缩短分数、细胞内Ca ²⁺信号和L型Ca ²⁺电流。还通过蛋白质印迹法测定蛋白质表达水平。电针治疗使存活率提高，并且上调的心脏肥大标志物显着减弱。 ISO 组的肌细胞缩短分数和松弛率降低，而 EA 显着改善了这些变化。与ISO大鼠相比，ISO + EA大鼠的心室肌细胞表现出较低的舒张期Ca ²⁺水平、较高的Ca ²⁺瞬变、较短的Ca ²⁺衰减和较高的L型Ca ²⁺电流。蛋白质表达分析表明，上调的 p-PLB 和 p-CaMKII 表达通过 EA 处理得以恢复，这表明 ISO + EA 大鼠心脏中的钙处理得到改善。此外，ISO大鼠的NOX2蛋白p-22 ^phox和p47 ^phox亚基的表达显着增加。给予 EA 后，p22 ^phox亚基的表达减少，而 p47 ^phox的减少并未达到显着水平。 ROS 增加会损害心肌细胞的 Ca ²⁺稳态和收缩活性，而长期 EA 给药可通过减少氧化应激来预防与病理性心脏肥大相关的 Ca ²⁺失调和功能异常。