血管紧张素Ⅱ介导心肌成纤维细胞增殖的信号转导

Signaling transconduction mediated cultured rat cardiac fibroblasts proliferation by angoitensin Ⅱ

目的探讨钙调神经磷酸酶（ＣａＮ）依赖的信号通路在血管紧张素Ⅱ（ＡｎｇⅡ）刺激的乳鼠心肌成纤维细胞（ＦＢｓ）增殖中的作用。方法以培养的ＦＢｓ为模型，用ＡｎｇⅡ刺激ＦＢｓ外Ｃａ２＋入流，环抱素Ａ（ＣｓＡ）阻断ＣａＮ信号通路，维拉帕米（Ｖｅｒ）阻断ＦＢｓ钙通道，检测ＦＢｓ ＣａＮ、丝裂素活化蛋白激酶（ＭＡＰＫ）、蛋白激酶 Ｃ（ＰＫＣ）活性，用［３Ｈ］－亮氨酸及［３Ｈ］－胸腺嘧啶参入量作为反应 ＦＢｓ增殖的指标。结果Ａｕｇ Ⅱ刺激组ＦＢｓ蛋白核酸合成速率明显增高，与对照组相比差异有显著性（Ｐ＜０．０１）；ＣｓＡ及Ｖｅｒ能明显抑制Ａｎｇ Ⅱ介导的ＦＢｓ蛋白核酸合成速率增高，与ＡｎｇⅡ血刺激组相比差异有显著性（ Ｐ＜ ０． ０１）。同时发现 Ａｎｇ Ⅱ刺激组 ＣａＮ、ＰＫＣ活性与对照 ＦＢｓ相比差异有显著性（ Ｐ＜ ０． ０５或 Ｐ＜０．０１）。 ＣｓＡ和Ｖｅｒ抑制ＡｎｇⅡ介导的 ＦＢｓ ＣａＮ活性增高，Ｖｅｒ抑制Ａｎｇ Ⅱ介导的ＦＢｓＰＫＣ活性的增高。结论 ＣａＮ信号通路在ＡｎｇⅡ刺激的ＦＢｓ增殖中起重要作用，但ＣａＮ信号通路不是ＡｎｇⅡ介导ＦＢｓ的增殖的唯一信号通路，以ＭＡＰＫ为核心的信号通路亦参与了ＡｎｇⅡ刺激的ＦＢｓ增殖。

AIM To study the effect of calcineurin (CaN)-dependent sighing passway on proliferation of rat cardiac fibroblasts (FBs) uhder stimulation of angoitensin H (Ang Ⅱ ). METHODS Upon the model of cultured rat FBs, Ca2+ influx stimulated with Aug Ⅱ, CaN signaling pathway was blocked with cyclosporine A (CsA ) and Ca2+ channel with verapamil(Ver), detecting the activities of FBs CaN, mitogen activated protein kinase (MAPK) and protein kinase C(PKC), [3H]-leucine([3H]-Leu) and [3H]-thymidine([3H]-TdR) incorporation as the target to evaluate FBs Proliferation. RESULTS Synthesis rates of protein and nucleic acid stimulated by Ang Ⅱ in FBs increased significantly in contrast to control (P < 0. 01 ); CsA and Ver markedly inhibited syntheses of protein and nucleic acid mediated by Ang Ⅱ in FBs with a significant difference from Ang Ⅱ stimulated group (P< 0 .01 ). CsA and Ver also sup- pressed FBs on activity mediated by Ang Ⅱ, and Ver suppressed are PKC activity mediated by Ang Ⅱ. CONCLUSION The study indicates CaN signaling pathway play an important role in FBs prolifera- proliferation induced by Ang Ⅱ, but it is not the single signaling pathway in regulating FBs proliferation, MAPK-centered signaling pathway is also involved in FBs proliferation induced by Aug Ⅱ.