钙调神经磷酸酶信号通路在AngⅡ刺激的大鼠VSMCs增殖中的作用

目的:探讨钙调神经磷酸酶（calcineurin,CaN）依赖的信号通路在血管紧张素Ⅱ（Ang Ⅱ）刺激的大鼠血管平滑肌细胞（VSMCs）增殖中的作用。方法:采用组织贴块法,体外原代培养大鼠胸主动脉平滑肌细胞;Ang Ⅱ刺激培养的大鼠 VSMCs增殖;CaN特异性抑制剂环孢素 A（CsA）阻断Ang Ⅱ刺激的大鼠VSMCs中CaN依赖的信号转导通路;观察各因素对CaN活性、细胞增殖活度、增殖细胞核抗原（PCNA）表达水平的影响。结果:在一定范围内,Ang Ⅱ（10-8～10-6mol/L）以浓度依赖性方式增加VSMCs的CaN活性,同时细胞增殖活度（AMTT值）增高,与对照组相比,差异有统计学意义（P<0.01或P<0.001）。CsA（1 μmol/L）抑制CaN活性后,明显降低Ang Ⅱ（10-7mol/L）刺激的VSMCs增殖活度及核内PCNA的表达水平（OD值）,与Ang Ⅱ组比较,差异显著（P<0.001）。结论:CaN依赖的信号通路在Ang Ⅱ刺激的血管平滑肌细胞增殖中发挥重要作用。

Role of Calcineurin Signal Pathway in the Proliferation of Rat VSMCs Stimulated by Angiotensin Ⅱ

Objective: To explore the role of calcineurin (CaN)-dependent signal transduction pathway in the proliferation of rat vascular smooth muscle cells (VSMCs) stimulated by angiotensin Ⅱ. Methods: Rat VSMCs were cultured in vitro using tissuepiece-anchorage primary culture. Rat VSMCs were treated with angiotensin Ⅱ (Ang Ⅱ) to form cellproliferation model. Cyclosporin A(CsA) ,an specific inhabitor of CaN, was used to block CaN-depended signal transduction pathway in rat VSMCs stimulated by Ang Ⅱ. To observe the effect of different agent on CaN activity, proliferation activity and theexpression of proliferating cell nuclear antigen (PCNA) . Results: Within a certain concentration coverage, Ang Ⅱ (10-8 - 10-6 mol/L) increased CaN activity of VSMCs by a dose-dependent way, meanwhile, increased the proliferation activity (AMTT value) of VSMCs with markedly statistics difference (P<0.01 or P<0.001) comparing with the control. Cyclos-porin A (CsA, 1 umol/L) decreased the proliferation activity and the expression levels (OD value) of PCNA in VSMCs stimulated by Ang Ⅱ (10-7 mol/L) with significant difference ( P < 0.001) , compared with Ang II group. Conclusion: Calcineurin-dependent signal pathway played an important role in the proliferation of cultured rat vascular smooth muscle cells stimulated by angiotensin Ⅱ.