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目的:观察阿托伐他汀和卡托普利干预对连续周期性波动的高静水压下大鼠肾小球系膜细胞(MC)产生PAI-1和tPA的影响。方法:大鼠MC分别在生理压力(5.32kPa,PP)、中压(7.98kPa,MP)、高压(10.64kPa,HP)环境下,不同药物(阿托伐他汀、卡托普利)中培养1、3、5、7d。Western Blotting法测定细胞裂解液中组织型纤溶酶原激活物(tPA)、纤溶酶原激活物抑制物1(PAI-1)含量。结果:与PP组1d相比,PP组3、5、7dtPA、PAI-1水平无明显变化;MP和HP组从1d开始可见PAI-1水平呈时间依赖性升高,7d达到最高。tPA呈时间依赖性下降,MP、HP组在1d开始下降,7d达到最低。阿托伐他汀和卡托普利均能抑制MP、HP组PAI-1水平上升及tPA水平下降,2者合用可进一步抑制PAI-1水平上升及tPA水平下降。结论:周期性波动的高静水压可使PAI-1水平上升,tPA水平下降。阿托伐他汀和卡托普利可缓解高静水压引起的PAI-1上升,tPA下降,2者存在协同作用。
AIM: To investigate the effects of atorvastatin and captopril on the production of PAI-1 and tPA in rat mesangial cells (MCs) under continuous hydrostatic pressure with continuous cyclical fluctuations. METHODS: Rat MCs were cultured in different drugs (atorvastatin, captopril) under physiological pressure (5.32kPa, PP), medium pressure (7.98kPa, MP) and high pressure (10.64kPa, 1,3,5,7 d. The contents of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in cell lysate were determined by Western Blotting. Results: The levels of 3,5,7dtPA and PAI-1 in PP group did not change significantly compared with those in PP group. The levels of PAI-1 in MP group and HP group increased from the 1st day to the 7th day. The time-dependent decline of tPA, MP, HP group began to decline in 1d, reached the lowest 7d. Both atorvastatin and captopril could inhibit the increase of PAI-1 level and tPA level in MP and HP group. The combination of both could further inhibit the increase of PAI-1 level and the decrease of tPA level. CONCLUSION: The high hydrostatic pressure with periodic fluctuations can increase the level of PAI-1 and decrease the level of tPA. Atorvastatin and captopril alleviate the high hydrostatic pressure caused by increased PAI-1, tPA decreased, there is synergy between the two.