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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 ,AT1a的拮抗剂有望为阻止肝纤维化发展提供新策略
Objective: To investigate the effect of angiotensin II and its antagonist losartan, a type 1 receptor (AT1a) antagonist, on collagen synthesis in hepatic stellate cells. Methods: ①The isolation, culture and identification of rat hepatic stellate cells; ② The hepatic stellate cells were detected by [3 H] -proline incorporation and release assay under the action of different concentrations of angiotensin II and losartan Cells produce collagen. Results: ① The cell yield was 2 × 10 7- 3 × 10 7 cells / cell, the viability was over 95% and the purity was over 90%. ② Angiotensin II produced a significant increase of collagen production in hepatic stellate cells (P <0.05) at a concentration of 10 -6 mol / L - 10 -10 mol / L, and a positive correlation between the concentration of angiotensin II and collagen = 0 96 0, P <0 0 1). Losartan significantly decreased collagen production (P <0.05) at a concentration of 10 -6 mol / L - 10 -9 mol / L and a negative correlation with collagen production (r = - 0 882, P < 0 0 1). CONCLUSION: Angiotensin II can induce a large amount of collagen production in hepatic stellate cells. Losartan significantly reduces collagen synthesis after antagonizing AT1a, suggesting that angiotensin II plays an important role in the development of hepatic fibrosis Antagonists of AT1a are expected to provide new strategies for preventing the development of hepatic fibrosis