钙调神经磷酸信号通路参与心肌成纤维细胞的增殖

目的 :探讨钙调神经磷酸酶 （Ca N）依赖的信号通路在三磷酸肌醇 （IP3 ）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 IP3 刺激 FBs内 Ca2 +释放 ,环孢素 A（Cs A）阻断 Ca N,维拉帕米 （Ver）阻断 FBs钙通道 ,检测 FBs Ca N、丝裂素活化蛋白激酶 （MAPK ）、蛋白激酶 C（PKC）活性 ,用 3 H-亮氨酸及 3 H-胸腺嘧啶掺入量作为反映 FBs增殖的指标。结果 :IP3 刺激组 FBs蛋白核酸合成速率明显增高 ,与对照组相比差异显著 （P<0 .0 1） ;Cs A及 Ver能明显抑制 IP3 介导的 FBs蛋白核酸合成速率增高 ,与 IP3 刺激组相比差异显著 （P<0 .0 1）。同时发现 IP3 刺激组 Ca N、PKC活性与对照 FBs相比差异显著 （P<0 .0 5或 P<0 .0 1）。 Cs A和 Ver抑制 IP3 介导的FBs Ca N活性增高 ,Ver抑制 IP3 介导的 FBs PKC活性的增高。结论 :Ca N在 IP3 刺激的 FBs增殖中起重要作用 ,其它信号通路可能也参与了 IP3 刺激的 FBs增殖

Calcineurin signaling pathway involved in cultured rat cardiac fibroblasts proliferation

AIM:To study the effect of calcineurin (CaN)-dependent signaling passway on proliferation of rat cardiac fibroblasts(FBs) under stimulation of inositol(1,4,5)-trisphosphate(IP 3).METHODS:On the model of cultured rat FBs,Ca 2+ influx was stimulated with IP 3;CaN signaling pathway was blocked with cyclosporine A(CsA) and Ca 2+ channel with verapamil (Ver),so as to detect 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 was used as the target to evaluate FBs proliferation. RESUTLS:Synthesis rates of protein and nucleic acid stimulated by IP 3 in FBs increased significantly in contrast to the control(P<0.01);CsA and Ver markedly inhibited the syntheses of protein and nucleic acid mediated by IP 3 in FBs with a significant difference from IP 3-stimulated group (P<0.01). CsA and Ver also suppressed FBs CaN activity mediated by IP 3,and Ver suppressed FBs PKC activity mediated by IP 3. CONCLUSION:CaN signaling pathway plays an important role in FBs proliferation induced by IP 3, and other signaling pathways may be involved in FBs proliferation induced by IP 3?