Lisinopril和Losartan对乳鼠心脏成纤维细胞AT1受体基因表达水平和ACE活力的影响

为了解两种降压药物 -血管紧张素转换酶 (angiotensin converting enzyme,ACE)抑制剂(lisinopril)和血管紧张素 型受体 (AT1 R)拮抗剂 (losartan)在心脏间质组织中的作用 ,进行了药物对乳鼠心脏成纤维细胞 AT1 R基因表达和血管紧张素转换酶活力影响的实验 .用 RT- PCR方法检测体外培养乳鼠心脏成纤维细胞 AT1 R基因的表达 .结果显示 ,losartan在 1 0 -7～ 1 0 -4 mol/L浓度范围内对心肌成纤维细胞 AT1 R基因表达有激活作用 ,其中 1 0 -5mol/L浓度激活作用最强 ;1 0 -5mol/L losartan对 AT1 R基因表达呈现明显的时间依赖性变化 ,当加入 1 h后 ,AT1 R基因表达量增加 2倍 ,随后出现一过性下降 ,2 4 h时回升并维持在一较高水平 .与 losartan相比 ,lisinopril对 AT1 R基因的表达无明显影响 .酶活实验结果显示 ,lisinopril明显抑制心肌成纤维细胞中的ACE活力 ,随时间延长 ,酶活力逐渐恢复 (1 2 .6× 1 0 -3 U/mg) ;而 losartan则对酶活力的影响不明显 ,仅是在 1 2 h后 ,ACE活力才略有升高 .实验结果证明 ,在心脏成纤维细胞中存在有 ACE和AT1 R,并且后者受 losartan以浓度和时间依赖方式的调节 .

The Effects of Lisinopril and Losartan on AT1 Receptor Gene Expression and ACE Activity of Neonatal Rat Cardiac Fibroblasts

In order to understand the effects of two drugs,angiotensin converting enzyme inhibitor(lisinopril) and angiotensin Ⅱ type 1 receptor(AT1R)antagonist(losartan)in cardiac interstitial tissue,the experiments of detecting AT1R gene expression and ACE activity from neonatal rat cardiac fibroblast were carried out.AT1R gene expression had been detected by RT PCR method,the results showed that in a range of concentrations(10 -7 -10 -4 mol/L),losartan stimulated the AT1R gene expression of cardiac fibroblast.In 10 -5 mol/L losartan,the expression of fibroblast AT1R gene displayed a dynamic change process according to time alteration.At the beginning,AT1R gene expression level was raised quickly and reached a two fold level after 1 hour,soon afterwards decreased transiently,and at 24 hours expression level rose again and kept at a quite high level.In contrast,lisinopril had no obvious effect on AT1R gene expression.Lisinopril inhibited the cardiac fibroblast ACE activity obviously,but as time passed by,enzyme activity was recovered(12.6 mU/mg)gradually.Losartan had no effect on ACE activity,only a little increase of enzyme activity appeared at 12 hours.It was confirmed that cardiac fibroblasts contained ACE and AT1R,and the expression of AT1R gene was regulated by concentration and action time of losartan.