血管紧张素Ⅱ对不同年龄大鼠的促心肌肥厚作用

The effect of angiotensin Ⅱon cardiac hypertrophy in SD rat with different ages

目的 探讨血管紧张素Ⅱ (AngⅡ )在不同年龄SD大鼠致心肌肥厚作用的特点及机制。 方法 应用心肌细胞和心肌成纤维细胞体外培养 ,分别测定心肌细胞3 H 亮氨酸 (3 H leu)掺入和心肌成纤维细胞3 H 胸嘧啶脱氧核苷 (3 H TdR)掺入 ,观察AngⅡ对不同年龄SD大鼠心肌细胞蛋白合成和心肌成纤维细胞分裂增殖的影响及心肌成纤维细胞对心肌细胞蛋白合成的作用。 结果 10 6mol/L的AngⅡ可使新生SD大鼠的心肌细胞3 H leu掺入明显增加 (P <0 0 5 )。加入心肌成纤维细胞培养上清液后 ,新生乳鼠心肌细胞3 H leu掺入增加更显著 (P <0 0 1) ,但不能增加 12月龄组心肌细胞3 H leu的掺入 ;10 6mol/LAngⅡ可使新生和 12月龄两组SD鼠心肌成纤维细胞3 H TdR掺入均显著增加 (P <0 0 1) ,Losartan可阻断上述AngⅡ的作用。 结论 AngⅡ通过AngⅡ 1型受体 (AT1)受体对新生乳鼠心肌细胞和心肌成纤维细胞具有直接促蛋白合成及细胞分裂作用 ,并可通过心肌成纤维细胞进一步促进心肌肥大。随年龄增长 ,AngⅡ主要影响心肌成纤维细胞分裂增殖 。

Objective The effect of angiotensinⅡ(AngⅡ) on cardiac hypertrophy were studied in SD rat with different ages. Methods Cardiocyte and cardiac fibroblasts in neonatal SD rat group and 12 months SD rat group were cultured in vitro. In each ages group, control MEM, angⅡ, angⅡantagonist(Losartan) and angⅡ+losartan were administrated respectively. 3 H leu incorporation into cardiocyte and 3 H TdR incorporation into cardiac fibroblasts were measured in neonatal rat group and 12 month rat group. To investigate the effect of cardiac fibroblasts on cardiocyte under the influence of angiotensinⅡ, the supernatant of cultured cardiac fibroblasts with angiotensinⅡ, the supernatant of cultured CBS with losartan and the supernatant of cultured cardiac fibroblasts with angiotensinⅡ and Losartan were added into cultured cardiocyte respectively. 3 H leu incorporation into cardiocyte were tested. Results 10 6 mol/L angⅡcan evidently augment 3 H leu incorporation into cardiocyte ( P <0 05) in neonatal rat group, not in 12 month group. Moreover, The supernatant of cultured cardiac fibroblasts with angiotensinⅡcan increase the 3 H leu incorporation into cardiocyte more evidently( P <0 01) in neonatal rat group. 10 6 mol/L of angiotensin Ⅱ can obiviously increase 3 H TdR incorporation into cardiac fibroblasts in neonatal group and 12 month group ( P <0 01). The effects of angⅡ were completely blocked by losartan with the same mmol concentration. Conclusions AngⅡcan directly increase protein synthesis of cardiocyte and the number of cardiac fibroblasts by activating AT1 receptor in neonatal SD rat. Moreover, cardiac fibroblasts with angⅡ can further induce cardiocyte protein synthesis by secreting some effective factors. AngⅡmainly influences proliferation of cardiac fibroblasts with aging. The usage of AT1 receptor antagonist can block these effects of angⅡ and prevent cardiac hypertrophy, especially interstitial hypertrophy.