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(5.32 kPa,PP)、中压(7.98 kPa,MP)、高压(10.64 kPa,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、7d tPA、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。
Objective:To investigate the effects of atorvastatin and captopril on the level of PAI-1 and tPA of rat mesangial cells (RMC) under continual high hydrostatic pressure. Method:RMCs were exposed to physiological pressure (PP), moderate pressure (MP), high pressure (HP) in 1,3,5,7 days respectively. Each pressure condition was enrolled in five groups : control, captopril (10 μmol/L), atorvastatin (10 μmol/L), captopril+ atorvastatin (10 μmol/L+ 10 μmol/L) and dimethylsulfoxide group. Content of PAI-1 and tPA were investigated with Western blotting in supernatant of lysate. Result:Compared with 1st day of PP, the level of PAI-1 was elevated significantly from 1st day on MP and HP, and achieved the highest level at 7th day. Conversely, tPA was decreased significantly in MP, HP, from 1st day to 7th day. Both atorvastatin and captopril could partly inhibit the elevation of level of PAI-1 and the reduction of level of tPA. Atorvastatin together with captopril could decline PAI-1 and rise tPA. Conclusion: Recurrent fluctuant static pressure above physiological pressure can elevate the level of PAI-1 and decrease the level of tPA. Both atorvastatin and captopril can decrease PAI-1 and increase tPA. Captopril and atorvastatin have a synergistic action.