摘要
目的 :建立心肌细胞肥大模型 ,观测正常与肥大心肌细胞对血管紧张素Ⅱ (AngⅡ )促凋亡刺激的易感性 .方法 :采用新生大鼠原代培养心肌细胞 ,观测内皮素 (ET 1)或AngⅡ单独作用 2 4h后 ,心肌细胞面积与凋亡率的变化 .进一步观测ET 1作用 2 4h后 ,再用AngⅡ刺激 2 4h ,心肌细胞凋亡率的变化 .结果 :① 10或 10 0nmol·L-1ET 1作用 2 4h ,心肌细胞轮廓面积较对照组分别增加 16 8%或 184 %.而凋亡率分别为 10 .9%或 11.7%,与对照组 (10 .7%)相比均无显著性差异 .② 0 .1,1.0或 10 .0nmol·L-1AngⅡ单独作用2 4h ,心肌细胞的面积较对照组分别增大了 14 6 %,16 2 %或2 2 4 %.其凋亡率则分别为 12 .6 %,17.2 %或 16 .2 %,均与对照组有显著性差异 .③经 10nmol·L-1ET 1处理 2 4h后 ,再用 1nmol·L-1AngⅡ作用 2 4h ,心肌细胞的凋亡率进一步增加为 2 1.6 %,与对照组或 1.0nmol·L-1AngⅡ刺激组相比 ,均具有显著性差异 .④AngⅡ的AT1受体阻滞剂Losartan既可抑制AngⅡ诱导的正常心肌细胞凋亡 ,亦可抑制肥大心肌细胞的凋亡 .而AT2 受体阻滞剂PD12 3319则无明显作用 .结论 :ET 1具有剂量依赖性促心肌细胞肥大作用 ,而对心肌细胞凋亡率无明显影响 .AngⅡ有剂量依赖性促心肌细胞肥大作用和非剂量依赖性促心肌细胞凋亡?
AIM: To set up a hypertrophic cardiomyocyte model in vitro and to observe the susceptibility to angiotensin Ⅱ induced apoptosis in normal and hypertrophic cardiomyocytes. METHODS: Primarily cultured rat cardiomyocytes were treated for 24 h with endothelin 1 (ET 1) and angiotensin Ⅱ (Ang Ⅱ) respectively or first ET 1 followed by Ang Ⅱ. After treatment, profile area and apoptotic rate were measured. RESULTS: ① Myocytes treated with 10 or 100 nmol·L -1 ET 1 for 24 h showed a 168% or 184% significant increase in profile area compared with control. On the other hand, no difference in apoptosis rate was found between both groups (10.9% and 11.7%, respectively) and control (10.7%). ② Myocytes treated with 0.1, 1.0, or 10.0 nmol·L -1 Ang Ⅱ for 24 h showed 146%, 162% or 224% increase in profile area compared with control, and the apoptosis rate increased to 12.6%, 17.2%, or 16.2%, respectively. ③ The apoptosis rate increased to 21.6% when myocytes were exposed to 10 nmol·L -1 ET 1 for 24 h and afterwards to 1.0 nmol·L -1 Ang Ⅱ for another 24 h. There was a significant increase in apoptosis rate compared with control or 1.0 nmol·L -1 Ang Ⅱ treatment groups. ④ In both groups of myocytes, the AT 1 receptor blocker losartan completely inhibited the consequences of Ang Ⅱ. Conversely, the AT 2 receptor antagonist PD123319 had no effect on Ang Ⅱ induced apoptosis. CONCLUSION: ET 1 has a dose dependent pro hypertrophic effect on cardiomyocytes, but no pro apoptotic effect on cells. The Ang Ⅱ also has a dose dependent pro hypertrophic effect on cardiomyocytes. Ang Ⅱ can increase cardiomyocytes apoptosis rate, which is more significant in hypertrophic cells than in normal cells.
出处
《第四军医大学学报》
北大核心
2003年第12期1070-1074,共5页
Journal of the Fourth Military Medical University
基金
国家教育部高等学校骨干教师资助计划
