摘要
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
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?
出处
《心脏杂志》
CAS
2002年第3期181-183,共3页
Chinese Heart Journal
基金
四川省科委资助项目 ( 2 0 0 0 14 5 )
