血管紧张素II和洛沙坦对肝星状细胞合成胶原的影响

Effects of angiotensin II and losartan on collagen synthesis in rat hepatic stellate cells

目的 :探讨血管紧张素II及其 1型受体 (AT1a)拮抗剂洛沙坦 (losartan) ,对肝星状细胞合成胶原的影响。方法 :①大鼠肝星状细胞的分离、培养及鉴定 ;②在不同浓度的血管紧张素II和洛沙坦作用下 ,采用 [3 H]-脯氨酸掺入释放法分别检测肝星状细胞生成胶原的情况。结果 :①细胞得率为 2× 10 7- 3× 10 7个 /只 ,活力在 95 %以上 ,纯度超过 90 %。②血管紧张素II在浓度为 10 -6mol/L - 10 -10 mol/L时 ,肝星状细胞生成胶原明显增多 (P <0 0 5 ) ;血管紧张素II浓度与胶原量呈正相关 (r=0 96 0 ,P <0 0 1)。洛沙坦在浓度为 10 -6mol/L - 10 -9mol/L时 ,胶原生成量显著减少 (P <0 0 5 ) ;且浓度与胶原生成量呈负相关 (r=- 0 882 ,P <0 0 1)。结论 :血管紧张素II可以促使肝星状细胞产生大量的胶原 ;洛沙坦通过拮抗AT1a后 ,胶原合成量显著减少 ,提示血管紧张素II在促使肝纤维化的发展过程中起着重要的作用 。

AIM: To investigate the effects of angiotensin II (Ang II) and AT_(1a) receptor antagonist (losartan) collagen synthesis in rat hepatic stellate cells (HSCs). METHODS: ① Rat HSCs were isolated, cultured and identified. ② Rat HSCs were incubated in the medium with different concentrations of AngII or losartan, then the quantity of collagen was examined by [~3H]-proline release assay. RESULTS: ① The yield of HSCs was 2×10~7-(3×10~7/per) rat, their viability and purity was more than 95% and 90%, respectively. ② The yield of collagen in HSCs significantly got a rise in a concentration-dependent manner when HSCs were incubated with AngII (10^(-6)mol/L-10^(-10) mol/L) (P<0.05). While HSCs were influenced by the antagonist of AT_(1a) (10^(-6) mol/L-10^(-9) mol/L), the quantity of collagen dropped greatly (P<0.05). CONCLUSIONS: Ang II stimulates HSCs to produce more collagen. Losartan inhibits the cell to synthesize collagen via AT_(1a) receptor (P<0.05). The results indicate that Ang II may play an important role in the development of hepatic fibrosis, and use of AT_(1a) antagonist may offer a new strategy to prevent hepatic fibrosis. [