血管紧张素1-7抑制血管外膜成纤维细胞增殖

Impact of Angiotensin-(1-7) on the Proliferation in Cultured Rat Adventitial Fibroblasts

目的 探讨血管紧张素1 -7对血管外膜成纤维细胞增殖的影响。方法 在培养大鼠血管外膜成纤维细胞中,用血管紧张素Ⅱ和血管紧张素1 7刺激,检测蛋白激酶C、丝裂素活化蛋白激酶及钙调神经磷酸酶活性,以氚标胸腺嘧啶和氚标亮氨酸掺入量反映血管外膜成纤维细胞增殖的指标。结果 血管紧张素1 -7既能明显抑制基础状态下血管外膜成纤维细胞蛋白激酶C、丝裂素活化蛋白激酶和钙调神经磷酸酶活性(P <0 .0 1或P <0 .0 5 ) ,又能抑制血管紧张素Ⅱ刺激下的血管外膜成纤维细胞蛋白激酶C、丝裂素活化蛋白激酶和钙调神经磷酸酶活性(P <0 .0 1或P <0 .0 5 )。血管紧张素1 7能明显抑制血管外膜成纤维细胞氚标胸腺嘧啶和氚标亮氨酸掺入(P <0 .0 1或P<0 .0 5 ) ;而血管紧张素Ⅱ则促进血管外膜成纤维细胞氚标胸腺嘧啶和氚标亮氨酸掺入(P <0 .0 1或P <0 .0 5 )。血管紧张素1- 7还能抑制血管紧张素Ⅱ刺激下的血管外膜成纤维细胞氚标胸腺嘧啶和氚标亮氨酸掺入(P <0 .0 1或P <0 .0 5 )。结论 血管紧张素1- 7可能通过影响蛋白激酶C、丝裂素活化蛋白激酶和钙调神经磷酸酶信号通路,发挥抑制血管外膜成纤维细胞增殖的作用。

Aim To investigate the effect of Angiotensin-(1-7)[ Ang-(1-7)]on the activities of protein kinase C (PKC), migogen-activated protein kinase (MAPK) and calcineurin (CaN) in cultured rat adventitial fibroblasts to affect proliferation. Methods PKC, MAPK and CaN activities were measured in cultured rat adventitial fibroblasts, the proliferation was examined by 3H-Thymidine (3H-TdR) and 3H-Leucine (3H-Leu) incorporation. Results By contrast, AngⅡ promoted PKC, MAPK and CaN activities in cultured rat adventitial fibroblasts (P<0.01 or P<0.05). Ang-(1-7) not only inhibited PKC, MAPK and CaN activities, but also decreased AngⅡ mediated PKC, MAPK and CaN activities, compared with their respective controls (P<0.01 or P<0.05). AngⅡ increased 3H-TdR and 3H-Leu incorporation in cultured rat adventitial fibroblasts, Ang-(1-7) not only inhibited 3H-TdR and 3H-Leu incorporation, but also decreased 3H-TdR and 3H-Leu incorporation mediated by AngⅡ in cultured rat adventitial fibroblasts, compared with their respective controls (P<0.01 or P<0.05). Conclusion It is concluded that Ang-(1-7) inhibited cultured rat adventitial fibroblasts proliferation by depressing PKC-MAPK and CaN signaling pathway