Zhang Yi-jun, Yang Xi-shan, Wu Ping-sheng, Li Xu, Zhang Xiao-feng, Chen Xiao-qing, Yu Zhong-xun
Second Department of Gerontology, Guangzhou General Hospital of Guangzhou Command, Guangzhou 510010, China.
Di Yi Jun Yi Da Xue Xue Bao. 2003 Mar;23(3):219-21, 227.
To investigate the effects of angiotensin II (AngII) and AT1a blocker losartan on growth and proliferation of rat hepatic stellate cells (HSCs).
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).
AngII (1 x 10(-9) to 1 x 10(-7) mol/L) stimulated HSC proliferation as demonstrated by cell counting, MTT assay and thymidine incorporation test (P < 0.05), but such effect was not observed at lower doses (<1 x 10(-9) mol/L). Losartan had significant inhibitory effect on HSC growth at the concentration of 1 x 10(-8) to 1 x 10(-6) mol/L (P < 0.05), but not at lower doses (<1 x 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).
Rapid proliferation of rat HSCs occurs in response to AngII treatment, but is inhibited after AT1a receptor is blocked with the antagonist losartan.
研究血管紧张素II(AngII)及AT1a受体阻滞剂氯沙坦对大鼠肝星状细胞(HSCs)生长和增殖的影响。
分离、培养并鉴定大鼠HSCs,然后用不同浓度的AngII或氯沙坦孵育。通过细胞计数和MTT法评估细胞生长和增殖情况,并用(3)H-胸腺嘧啶核苷掺入法((3)H-TDR)评估这些药物对HSC DNA合成的影响。
细胞计数、MTT法及胸腺嘧啶核苷掺入试验表明,AngII(1×10^(-9)至1×10^(-7)mol/L)可刺激HSC增殖(P<0.05),但较低剂量(<1×10^(-9)mol/L)时未观察到这种作用。氯沙坦在浓度为1×10^(-8)至1×10^(-6)mol/L时对HSC生长有显著抑制作用(P<0.05),但较低剂量(<1×10^(-8)mol/L)时无此作用。与对照组相比,氯沙坦和AngII共同刺激细胞并未导致细胞数量显著增加(P>0.05)。
大鼠HSCs在AngII作用下迅速增殖,但在用拮抗剂氯沙坦阻断AT1a受体后增殖受到抑制。