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目的 探讨成纤维细胞与血管紧张素 (AgⅡ )的关系及AgⅡ受体拮抗剂Losartan对人肾间质成纤维细胞 (HRIF)的作用。方法 分离培养的HRIF经鉴定后 ,利用3 H TDR掺入法、流式细胞仪及免疫组织化学技术观察了AgⅡ对HRIFDNA合成、细胞周期的影响及Losartan的抑制效应。结果 (1)AgⅡ 10 -10 M至 10 -6M均增加了HRIF3 H TDR掺入率 ,第 1、3天呈剂量依赖关系 (γ1=0 70 9,P <0 0 1;γ3 =0 80 6 ,P <0 0 1) ;不同质量浓度的Losartan(17 7,10 4M)均抑制了AgⅡ 10 -6M诱导的HRIFDNA合成 (P <0 0 1)。 (2 )AgⅡ (10 -8M至 10 -5M )明显促进了HRIFG1期向S期转化 (P <0 0 1) ,Losartan明显延迟了AgⅡ 10 -6M诱导G1期向S期转化 (P <0 0 1)。结论 AgⅡ能够直接诱导HRIF细胞的增殖 ;Losartan可阻抑AgⅡ诱导的HRIF细胞增殖。
Objective To investigate the relationship between fibroblasts and angiotensin Ⅱ (AgⅡ) and the effect of Losartan, an Ag Ⅱ receptor antagonist, on human renal interstitial fibroblasts (HRIF). Methods After HRIF was isolated and identified, the effects of AgⅡ on HRIFDNA synthesis, cell cycle and Losartan inhibition were observed by 3 H TDR incorporation, flow cytometry and immunohistochemistry. Results (1) Ag II 10 -10 M to 10 -6 M increased the incorporation of HRIF3 H TDR, with a dose-dependent relationship at day 1,3 (γ1 = 0 709, P <0.01; γ3 = 0 806 , P <0.01). Losartan (17 7, 104 M) with different concentrations inhibited Ag II 10 -6M induced HRIF DNA synthesis (P <0.01). (2) AgⅡ (10 -8 M to 10 -5 M) significantly promoted the transformation from HRIFG1 phase to S phase (P <0.01), and Losartan delayed the G1 phase to S phase transformation induced by AgⅡ 10 -6M 1). Conclusion AgⅡ can induce the proliferation of HRIF cells directly. Losartan can inhibit the proliferation of HRIF cells induced by AgⅡ.