醛固酮对系膜细胞合成纤溶酶原激活剂抑制物-1的影响  

Effect of aldosterone on the expression of plasminogen activator inhibitor-1 in renal mesangial cells:experiment with rat renal mesangial cells

作　　者：袁军[1] 贾汝汉[1] 包艳[1] 

机构地区：[1]武汉大学人民医院肾内科,湖北中医学院附属医院肾内科430060

出　　处：《中华医学杂志》2007年第34期2439-2442,共4页National Medical Journal of China

摘　　要：目的探讨醛固酮及阻断其受体后对系膜细胞生成纤溶酶原激活剂抑制物1(PAI-1)的影响。方法醛固酮单独刺激大鼠系膜细胞24 h 以及采用螺内酯阻断后,用 RT-PCR 观察系膜细胞 PAI-1 mRNA 的变化;用 Western 印迹方法检测细胞上清液中的 PAI-1;采用 ELISA 方法测定细胞上清液中转化生长因子β1(TGF-β1)的含量;采用激光共聚焦检测系膜细胞内的活性氧(ROS)水平。观察不同浓度及不同作用时间的醛固酮刺激系膜细胞对 PAI-1mRNA 的影响。结果醛固酮使系膜细胞 PAI-1 mRNA 及蛋白表达明显升高,同时升高了 TGF-β1的表达和细胞内的 ROS 水平。醛固酮使 PAI-1 mRNA 表达呈剂量依赖性增加。100 nmol/L 醛固酮刺激系膜细胞4 h 后 PAI-1 mRNA 表达才明显增加。加用螺内酯后使升高的 PAI-1、TGF-β1表达以及细胞内 ROS 恢复到正常水平。结论醛固酮能独立促进大鼠系膜细胞分泌 PAI-1的增加,同时醛固酮使 TGF-β1表达以及细胞内 ROS 水平升高,而这些都是通过盐皮质激素受体介导的。Objective To evaluate the effects of aldosterone （aid） on the expression of plasminogen activator inhibitor-1 （PAId） in renal mesangial cells （MCs） and the changes after aldosterone was blocked with spironolactone. Methods Rat MCs of the line HBZY-1 were cultured and divided into 5 groups： aid group, treated with aldosterone （ 1 μmol/L or 100 nmol/L）, aid combined with spironolactone 1 nmol/L for 24 hours, and control group. Anotfher cells were cultured and treated with aid 100 nmol/L for 0, 0.5, 1, 2, 4, 6, 8, and 24 h respectively or treated with aid of the concentrations of 10-5, 10-6, 10-7, 10 -8, 10 -9, 10 -10, pr 10 ^-11 mol/L. RT-PCR and Western blotting were used to dete4cty the mRNA and protein expression of PAId. Confoeal laser scanning microscopy was used to detect the ROS level in the MCs. The transforming growth factor-β1 （TGF-β1） level in the medium was detected by ELISA. Results The PAId mRNA and protein levels of the aid 100 nmol/L and 1μmol/L groups became 2 times and 1.8 times, and 1.7 times and 1.9 times respectively those of the control group （ all P 〈 0.01 ）. The PAId mRNA and protein levels of the aid ＋ spirolactone group were not significantly different from those of the control group （all P 〉 0.05 ）. The TGF-β1 levels of the 100 nmol/L and 1 μmol/L aldosterone groups were 147 pg/ml ± 27 pg/ml and 183 pg/ml ±25 pg/ml respectively, both significantly higher than that of the control group （75 pg/ml ±23 pg/ml, both P 〈 0.01 ）. The TGF-β1 levels of the groups with spirolactone were not significantly different from that of the control group （ both P 〉 0.05 ）. The ROS levels of the 1 μmol/L and 100 nmol/L aid groups were 4. 87 times and 4.77 times that of the control group （ both P 〈 0.01 ）, and the ROS levels of the groups with spirolaetone were 1.95 time and 1.66 times that of the control group （ both P 〉 0. 05 ）. 100 nmol/L aid time-dependently increased the PAI-1 level since 4 hours after exposure to aid （ all P 〈 0.05

关 键 词：醛固酮 受体 盐皮质激素 纤溶酶原激活物抑制物1 转化生长因子Β 

分 类 号：R692[医药卫生—泌尿科学]