洛伐他汀联合环孢素A对人外周血单个核细胞增殖、细胞因子表达及NK细胞毒作用的影响

目的 探讨洛伐他汀联合环孢素A（CsA)对体外培养的人淋巴细胞增殖、对某些细胞因子表达及NK细胞活性的影响。方法 Ficoll-Hypague密度梯度离心法提取人外周血单个核细胞（PBMC）;乳酸脱氢酶（LDH）释放试验测定细胞活性;^3H-标记甲基胸腺嘧啶（^3H-TdR)掺入法观察药物对细胞增殖及细胞毒作用的影响;ELISA-斑点法（ELISA-SPOT）检测细胞分泌的IL-2;放免法（RIA）测定细胞上清IFN-γ的浓度;半定量反转录-聚合酶链反应（RT-PCR）显示IL-2及IFN-γmRNA的表达。结果 洛伐他汀及CsA均可剂量依赖性地抑制体外培养的人淋巴细胞的增殖,IL-2和IFN-γ表达及NK细胞活性。两药联合使用具有协同作用。结论 他汀类药物可与CsA协同使用减缓移植排斥反应发生发展,延长移植物寿命。

Effects of lovastatin combined with cyclosporine A on cultured human peripheral blood mononuclear cells proliferation,cytokines expression and cytotoxicity

OBJECTIVE: To investigate the effects of lovastatin combined with cyclosporine A (CsA) on cultured human peripheral blood mononuclear cells (PBMC) proliferation, cytokines expression and cytotoxicity in vitro. METHODS: The PBMC was isolated by using Ficoll-Hypague density gradient centrifugation method and its viability was evaluated with LDH-release assay. The effects of lovastatin combined with CsA on cultured PBMC proliferation and cytotoxicity were observed in 3H-TdR incorporation assay. The levels of supernatant IFN-gamma and IL-2 were quantitated respectively with RIA and ELISA-SPOT assay. The IL-2 and IFN-gamma mRNA expressions were determined by RT-PCR. RESULTS: Both lovastatin and CsA inhibited PBMC proliferation, expression of IL-2 and IFN-gamma, and NK cell cytotoxicity in a dose-dependent manner. Combination of the two drugs produced synergism. CONCLUSION: Statins combined with cyclosporine A have a synergic effect and can delay the incidence and development of allograft rejection and prolong the graft life-span in animal models and clinical trials.