辛伐他汀对肺成纤维细胞和嗜酸粒细胞相互作用的干预研究

Effect of simvastatin on the interaction of lung fibroblasts and eosinophils

目的 :研究肺成纤维细胞 (FB)和健康人外周血嗜酸粒细胞 (EOS)共同培养对EOS存活率及产生细胞因子粒细胞 巨噬细胞集落刺激因子 (GM CSF)的影响 ,探讨FB在哮喘发病机制中的作用 ;比较辛伐他汀和地塞米松对FB与EOS相互作用的干预效果 ,研究辛伐他汀诱导FB凋亡并抑制EOS性炎症的作用 ,从而为治疗哮喘提供新的途径。方法 :将肺FB和健康人外周血EOS共同培养 ,分别加入辛伐他汀或地塞米松进行干预并与对照组进行比较 ,采用台盼蓝拒染法检测EOS存活率 ,酶联免疫吸附法 (ELISA)检测GM CSF含量 ,TdT介导dUTP缺口末端标记 (TUNEL)法检测FB凋亡。结果 :(1)共同培养组EOS存活率明显高于其它组 (82 2± 10 3 ) % ,加入辛伐他汀或地塞米松干预后 ,EOS存活率下降了几乎 5 0 %〔(3 6 9± 8 1) %〕 ,与其它各组比较均有显著差异 (P <0 0 0 1)。 (2 )共同培养组GM CSF含量最高为 (5 3 9 5± 88 6)ng·L-1,与其余各组比较均有显著差异 (P <0 0 0 1) ,加入辛伐他汀或地塞米松干预后其含量明显下降 ,为 (4 2 2± 4 6)ng·L-1。 (3 )辛伐他汀和地塞米松均能明显诱导FB凋亡〔(5 9 0± 2 6) %、(2 4 1± 4 6) %〕 ,与溶剂组及空白对照组相比均有显著差异。结论 :(1)肺FB在体外能明显提高外周血EOS存活率。 (2 )

Objective To study the effect of fibroblast(FB) on the eosinophil(EOS) viability and the GM?CSF production and the interfering effect of simvastatin on the interaction of FB and EOS in order to provide a new way to control asthma.Methods Fibroblast and eosinophil were co cultured and divided into different groups added either with simvastatin or dexamethasone.The eosinophil survivals were assessed by trypan blue exclusion method.GM?CSF levels in culture supernatants were measured by using enzyme linked immnosorbent assay system.FB apoptosis was detected by TUNEL assay.Results Co culture of FB and EOS enhanced the eosinophil viability significantly compared with other groups,and the enhanced EOS survival was reduced almost 50% by adding either simvastatin or dexamethasone.GM?CSF levels in co culture of FB and EOS was sig^nificantly higher than other groups and decreased along with the decrease of eosinophil viability.The apoptosis of FB was evident when simvastatin or dexamethasone was added for 72?h compared with control group and solvent group.Conclusions FB enhances eosinophil viability in vitro .Co?culture of FB and EOS increases the production of GM?CSF,which may explain the mechanism of increased EOS viability.Simvastatin restrains the interaction of FB and EOS and decrease the eosinophil viability and GM?CSF levels just like dexamethasone.Simvastatin induces the apoptosis of FB in vitro which may be the mechanism of simvastatin restraining the interaction of FB and EOS.