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血管紧张素II和洛沙坦对肝星状细胞生长、增殖的影响
Effects of angiotensin II and losartan on the growth and proliferation of hepatic stellate cells
【摘要】 目的探讨血管紧张素II(AngII)及其1型受体(AT1a)拮抗剂洛沙坦(losartan),对肝星状细胞(HSCs)生长、增殖的影响。方法①分离大鼠HSCs,培养及鉴定;②在不同浓度的AngII或losartan作用下,观察HSCs生长情况分别绘制细胞生长曲线、采用MTT法、3H-胸腺嘧啶核苷掺入释放法检测AngII或losartan对HSCs生长、增殖的影响。结果AngII刺激组在浓度高于10-9 mol/L时,与对照组相比HSCs数量明显增多,DNA含量显著增加(P<0.05 );losartan在浓度高于10-8 mol / L时,HSCs数量明显减少,DNA含量显著降低(P<0.05 );(losartan+AngII)组HSCs数量与对照组相比无显著性差异(P>0.05)。结论AngII可以促使HSCs迅速增殖,其拮抗剂losartan明显抑制HSCs的生长、增殖。
【Abstract】 Objective To investigate the effects of angiotensin II (AngII) and AT1a blocker losartan on growth and prolifera-tion of rat hepatic stellate cells (HSCs). Methods Rat HSCs were isolated, cultured and identified, followed by incubation with AngII or losartan at different concentrations. The cell growth and proliferation were assessed via cell counting and MTT assay, and the effects of the agents on HSC DNA synthesis evaluated by way of 3 H-thymidine incorporation ( 3 H-TDR). Results AngII (1×10 -9 to 1×10 -7 mol/L) stimulated HSC proliferation as demonstrated by cell counting, MTT assay and thymi-dine incorporation test (P<0.05), but such effect was not observed at lower doses (<1×10 -9 mol/L). Losartan had significant in-hibitory effect on HSC growth at the concentration of 1×10 -8 to 1×10 -6 mol/L (P<0.05), but not at lower doses (<1×10 -8 mol/L). Co-stimulation of the cells with losartan and AngII did not result in a significant increase in cell number as compared with the control group (P>0.05). Conclusion Rapid proliferation of rat HSCs occurs in response to AngII treatment, but is inhibited af-ter AT1a receptor is blocked with the antagonist losartan.
【Key words】 angiotensin II; losartan; cell proliferation; hepatic fibrosis;
- 【文献出处】 第一军医大学学报 ,Journal of First Military Medical University , 编辑部邮箱 ,2003年03期
- 【分类号】R575
- 【被引频次】13
- 【下载频次】116