血管紧张素Ⅱ诱导心肌细胞凋亡与增殖的时相特征及益气活血药对其影响

Time-Phase Changed Character of Cardiac Muscle Cell Apoptosis and Proliferation Induced by Angiotensin Ⅱ and Influences of TCM Herbs for Supplementing Qi and Activating Blood Circulation on It

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中文关键词: 血管紧张素Ⅱ 心肌细胞凋亡增殖益气活血药

英文关键词:AngiotensinⅡ cardiac muscle cell apoptosis proliferation Chinese herbs for supplementing qi and activating blood circulation

基金项目:国家自然科学基金资助项目(No.90209021)

作者	单位
郭书文	北京中医药大学159信箱,北京,100029
崔巍	北京中医药大学159信箱,北京,100029
王硕仁	北京中医药大学159信箱,北京,100029
牛福玲	北京中医药大学159信箱,北京,100029
王国华	北京中医药大学159信箱,北京,100029

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中文摘要:

目的动态观察心肌细胞在血管紧张素Ⅱ(AngⅡ)作用后细胞凋亡与增殖的变化情况及益气、活血中药对其的影响。方法用AngⅡ作用于培养的SD大鼠乳鼠心肌细胞,利用图像分析系统、流式细胞仪、生化测定等,观察作用不同时间心肌细胞的搏动幅度、节律、频率、蛋白质含量、细胞面积大小、细胞凋亡情况以及益气、活血药对其的影响。结果模型组于实验24～48h细胞搏动频率加快,以24h搏动幅度最大;24h心肌细胞面积增大,48h明显增大;蛋白质含量于实验24h增加,48h达到最高含量;细胞数量12～48h有增多趋势,而从24h有细胞凋亡,48～72h凋亡率逐渐增高,72h达到最高(P<0.05或P<0.01),说明心肌细胞在肥大增生为主期(24～48h)进入凋亡为主期(48～96h),益气、活血药均有良好的防治作用,尤以益气加活血药作用明显(P<0.05,P<0.01)。结论AngⅡ作用于心肌细胞后存在肥大增生时间窗与细胞凋亡时间窗的特征。细胞肥大增生为主时,可能出现心肌肥大,细胞凋亡可能是由心肌肥大向心力衰竭转变的机制之一;益气活血药对其有改善作用。

英文摘要:

ObjectiveTo observe the dynamic change of apoptosis and proliferation of cardiac muscle cells (CMC) after being induced by AngiotensinⅡ(AngⅡ), and the effect of TCM herbs for supplementing qi and/or activating blood circulation on it. Methods The cultured CMC of SD suckling rat were treated by AngⅡ, and the amplitude, rhythm and frequency of cell pulsation, the protein content, area size and apoptosis of cells at various phases as well as the influence of TCM herbs afterwards were determined by image pattern analysis system, flow cytometry and biochemical assay. Results In the model group, cell pulsation showed quickened frequency from the 24th to 48th hr after AngⅡ treatment with the highest amplitude at the 24th hr; the cell area enlarged at the 24th hr, the enlargement became evident at the 48hr. Cell content of protein increased at the 24th hr, which reached to its peak at the 48th hr; an increasing trend of cell number was shown from the 12th to 48th hr; cell apoptosis started to appear at the 24th hr, it increased gradually from the 48th to 72th hr, and reached to the peak at the 72th hr (P<0.05 or P<0.01). All the Chinese herbs, both for supplementing qi and/or activating blood circulation, especially when they were used in combination, showed favourable preventive and therapeutic effect on CMC (P<0.05 or P<0.01), either at the early phase (24—48th hrs)mainly manifesting hypertrophy and proliferation or the late phase (48—96th hrs) mainly manifesting apoptosis. Conclusion There exist characterized phasic windows of CMC after being treated by AngⅡ, the window of hypertrophy-proliferation phase and the window of cell apoptosis phase. When CMC were mainly in hypertrophic manner, myocardial hypertrophy may appear. Cell apoptosis may be one of the mechanisms for turning myocardial hypertrophy to heart failure, and it could be improved by Chinese herbs for supplementing qi and/or activating blood circulation.

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