血管钠肽抑制低氧诱导的心肌成纤维细胞的增殖和胶原合成 _医学论文.docVIP

血管钠肽抑制低氧诱导的心肌成纤维细胞的增殖和胶原合成 _医学论文 血管钠肽抑制低氧诱导的心肌成纤维细胞的增殖和胶原合成 _医学论文 作者：吕顺艳　朱妙章　郭海涛　于军 【关键词】 细胞分裂 关键词: 心钠素血管肽类低氧心肌/细胞学成纤维细胞细胞分裂胶原 摘 要:目的 观察血管钠肽（Vasonatrin peptide，VNP）对低氧状态下大鼠心肌成纤维细胞（CFs）增殖及胶原合成的影响，探讨其防治低氧所致心肌间质结构重建的作用机制. 方法 培养新生大鼠CFs，应用流式细胞仪分析细胞周期，以3 H-proline掺入率反映胶原合成速率. 结果 单纯低氧不改变CFs的细胞周期，但增加低浓度血清（25mL#12539L-1 ）作用基础上的细胞增殖指数PI（S+G2 /M）/（S+G2 /M+G0 /G1 ）（0.01），10 -6 mol#12539L-1 的VNP抑制低氧诱导的PI增加（0.01）.低氧可以增加基础胶原合成（增加19.6%，0.05），也增加低浓度血清（25mL#12539L-1 ）诱导的胶原合成速率（增加37.2%，0.01）.10-8 ～10-6 mol#12539L-1 的VNP浓度依赖性抑制低氧诱导的胶原合成速率（0.01）. 结论 低氧增加胶原合成以及血清刺激的CFs的增殖反应，VNP抑制上述作用，从而抑制低氧引起的心肌纤维化. 　　Keywords:atrial natriuretic factorblood vesselspeptidesanoxiamyocardium/cytologyfibroblastscell divisioncollagen 　　Abstract:AIM To investigate the influence of vasonatrin peptide（VNP）on hypoxia-induced proliferation and collagen synthesis in cultured cardiac fibroblasts（CFs）and the pre-ventive mechanism of VNP in the interstitium remodeling of　ischaemic heart diseases due to hypoxia.METHODS Neonatal rat CFs were obtained by enzymatic dissociation.Cell cycle kinetics of CFs was analyzed by flow cytometry.Collagen synthesis rate was determined by measuring3 H-pro-line incorporation rate.RESULTS Hypoxia（20～30mL#12539L-1 oxygen）alone for24h didn’t change the cell cycle of cells cultured on serum-free medium，but significantly in-creased the proliferation index ［（S+G2 /M）/（S+G2 /M+G0 /G1 ）］of CFs with low concentration serum（25mL#12539L-1 ）.VNP（10-6 mol#12539L-1 ）inhibited the effects of hypoxia on low concentration serum-induced proliferation（0.01）.Hypoxia increased basal（under nomoxide without serum）and low concentration serum-induced collagen syntheses（un-der nomoxide with25mL#12539L-1 serum）by19.6%（0.05）and37.2%（0.01）in CFs，respectively.In a concen-trate-dependent manner，VNP（10-8 ～10-6 mol#12539L-1 ）de-creased the incorporation of3 H-proline induced by hypoxia for24h（0.01）.CONCLUSION Hypoxia might en-hance serum-induced proliferation in CFs and increase basal and serum-induced col