摘要
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系膜细胞(RMC)增殖及其产生血管紧张素Ⅱ(AngⅡ)和转化生长因子β1(TGF-β1)的影响,并探讨其可能的作用机制。方法RMC分别在生理压力(40mm Hg,PP)、中压(60mm Hg,MP)、高压(80mm Hg,HP)环境下,不同药物(阿托伐他汀10μmol/L、卡托普利10μmol/L)中培养1、3、5、7d。4-甲基偶氮四唑蓝(MTT)法测定各时段细胞增殖量。放射免疫法测定细胞裂解液中AngⅡ浓度。Western Blotting法测定细胞裂解液中TGF-β1含量。结果与PP组1d相比,PP组3、5、7d MC增殖,但AngⅡ浓度、TGF-β1含量无明显变化;MP和HP组从1d开始可见明显细胞增殖(0·79±0·07,0·93±0·10vs0·58±0·05;P<0·05或P<0·01),并随时间延长而进一步升高,AngⅡ和TGF-β1水平在MP和HP组也呈压力依赖性升高[(AngⅡ:130·6±24·3,261·5±51·2vs73·1±10·1)pg/mLP<0·05或P<0·01;TGF-β1:(1·61±0·16,1·86±0·21vs1·00±0·08P<0·01)],7d达到最高。阿托伐他汀和卡托普利均能抑制中、高压力对RMC的上述影响,抑制细胞增殖,并使AngⅡ和TGF-β1水平下降。二者共同作用可进一步抑制细胞增殖,并使AngⅡ和TGF-β1水平进一步下降。结论高静水压能刺激RMC增殖,并引起AngⅡ及TGF-β1水平上升。阿托伐他汀和卡托普利均能部分抑制高静水压引起的AngⅡ增加,继而部分抑制TGF-β1产生。阿托伐他汀与卡托普利存在协同作用。
Objective To investigate the effects of atorvastatin and captopril on the proliferation of rat mesangial cells （RMCs） and the production of angiotensin Ⅱ （Ang Ⅱ ）, transforming growth factor β1 （TGF-β1） under continual high hydrostatic pressure, and explore the potential mechanism. Methods RMCs were exposed to physiological pressure （40 mm Hg, PP）, moderate pressure （60 mm Hg, MP）, and high pressure （80 mm Hg, HP） 1, 3, 5, 7 days respectively. Mesangial cells exposed under different pressure conditions were cultured with： control, captopril （ 10 μmol/L） , atorvastatin （ 10 μmol/L）, captopril＋atorvastatin （10 ＋ 10）μmol/L and dimethylsulfoxide. Cell proliferation was assessed with MTT method. Concentration of Ang Ⅱ was measured with radioimmunoassay in supernatant of lysate. The content of TGF-β1 were investigated with Western blotting. Results No alteration in cell proliferation of RMC after 3, 5, 7 day cultured in PP condition. However, cell proliferation in MP, HP group were significantly increased （P〈0.05） in a time-dependent manner. The concentration of Ang Ⅱ in supernatants was increased significantly （P〈0. 05） in associated with elevated level of TGF-β1 from 1st day and reached to the highest at 7th day （P〈0.05）. Both atorvastatin and captopril inhibit the adverse effects of high hydrostatic pressure on RMCs. Atorvastatin together with captopril inhibit cell proliferationand Ang Ⅱ , TGF-β1 more pronouncedly. Conclusion Periodic fluctuant hydrostatic pressure above physiological pressure stimulates the proliferation of RMC and the production of Ang Ⅱ , TGF-β1 , which was partially attenuated by atorvastatin and captopril.
出处
《高血压杂志》
CAS
CSCD
北大核心
2006年第1期46-51,共6页
Chinese Journal of Hypertension
基金
国家自然科学基金
编号30260037
关键词
系膜细胞
细胞外基质
阿托伐他汀
卡托普利
高静水压
Mesangial cell
Extracelluar matrix
Atorvastatin
Captopril
High hydrostatic pressure
