阿托伐他汀和卡托普利对高压培养下大鼠系膜细胞外基质的影响

Effects of atorvastatin and captopril on the extracellular matrix of rat mesangial cells cultured under high hydrostaticpressure

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(RMC)细胞外基质(ECM)的影响。方法RMC分别在生理压力(40mmHg,PP)、中压(60mmHg,MP)、高压(80mmHg,HP)环境下,不同药物(阿托伐他汀、卡托普利)中培养1、3、5、7d。采用Western Blotting法测定细胞裂解液中胶原Ⅰ和Ⅳ、纤维连结生长因子(FN)的含量。结果与PP组第1天相比,PP组第3、5、7天胶原Ⅰ/Ⅳ、FN浓度无明显变化;MP和HP组从第1天开始可见胶原Ⅰ/Ⅳ、FN水平呈时间依赖性升高,7d达到最高。阿托伐他汀和卡托普利均能抑制MP、HP组胶原Ⅰ/Ⅳ和FN水平上升,胶原Ⅰ在1d时,阿托伐他汀吸光度(A)值为1.06±0.12,1.16±0.14vs0.78±0.05;卡托普利A值为0.96±0.09,1.02±0.13vs0.71±0.06(P<0.05)。二者合用可使胶原Ⅰ/Ⅳ和FN水平进一步下降。结论周期性波动的高静水压可使ECM积聚。阿托伐他汀和卡托普利能减轻高静水压引起的ECM积聚。二者合用存在协同作用。

Objective To investigate the effects of atorvastatin and captopril on the extracelluar matrix（ECM） of rat mesangial cells （RMC） under continual high hydrostatic pressure. Methods RMCs were exposed to physiological pressure （40 mm Hg, PP）, moderate pressure （60 mm Hg, MP）, high pressure （80 mm Hg, HP ） 1,3,5,7 days respectively. Each pressure condition was satisfied in five groups： control,captopril （10μLmol/L）.atorvastatin （10 μmol/L）,captopril＋atorvastatin（10μmol/L-10μmol/L） and dimethylsulfoxide. The treatment group contentration of FN, coLLagen Ⅰ .Ⅳ were tested with western blotting in the supernatant of lysate. Results Compared with the 1^st day of PP, the level of collagen Ⅰ was elevated significantly from 1^st day on MP and HP, dchieved the highest level at 7^th day. The change of FN, collagen Ⅳ were similar to collagen Ⅰ. Both atorvastatin and eaptopril could partly inhibit the elevation of extracellular matrix （collagen Ⅰ： 1 d, atorvastatin： 1.06±0.12, 1.16±0.14 vs 0.78±0.05;eaptopril：0.96±0.09, 1.02±0.13 vs 0.71±0.06; P〈0.05）. Atorvastatin combined with captopril can decrease collagen Ⅰ ,collagen Ⅳ and FIN better. Conclusions The recurrent fluctuant static pressure above physiological pressure can induce the accumulation of ECM. Both atorvastatin and captopril can inhibit the deleterious effects of high hydrostatic pressure. Captopril and atorvastatin are synergistic.