炎性细胞因子对肺血管内皮细胞与肺成纤维细胞三维立体培养基质金属蛋白酶2的影响  

Effect of inflammatory cytokines on MMP 2 in three-dimensional culture of pulmonary vascular endothelial cells and lung fibroblasts

作　　者：李超然 闫蕾 王惠 王学锷 芦莎 谢琳霞 王青 朱运奎 于军  LI Chaoran;YAN Lei;WANG Hui;WANG Xue’e;LU Sha;XIE Linxia;WANG Qing;ZHU Yunkui;YU Jun;Ronald F Ertl(The Third Department of Respiratory and Critical Care Medicine,Xi’an International Medical Center Hospital,Xi’an 710100,China;不详)

机构地区：[1]西安国际医学中心医院呼吸与危重症医学三科,陕西西安710100 [2]西安国际医学中心医院临床实验中心,陕西西安710100 [3]美国内布拉斯加州大学医学中心重症医学部,内布拉斯加州奥马哈72662

出　　处：《陕西医学杂志》2023年第7期920-924,共5页Shaanxi Medical Journal

基　　金：陕西省科技计划项目(2018ZDXM-SF-068)。

摘　　要：目的:探讨炎性细胞因子在肺损伤和肺纤维化过程中与基质金属蛋白酶(MMPs)的相关性。方法:建立肺微血管内皮细胞(HPMEC)/肺成纤维细胞(HFL)+Ⅰ型胶原三维立体培养模型,以不同细胞因子刺激,采用明胶酶谱法检测MMP_(2)的活性,观察组肺细胞分泌MMP_(2),各种细胞因子与MMP_(2)之间,以及各细胞因子之间的相互作用。结果:HFL是产生MMP_(2)的主要细胞,在白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和中性粒细胞弹性蛋白酶(NE)的刺激下产生更多的MMP_(2),白细胞介素-6(IL-6)不诱导HFL产生MMP_(2),HPMEC只能产生极微量的MMP_(2),且各种细胞因子均不能诱导HPMEC产生更多MMP_(2)。HFL与HPMEC混合三维立体培养下,TNF-α、IL-1β、NE能诱导产生多量的MMP_(2)。结论:在HFL与HPMEC混合3D培养条件下,炎性细胞因子TNF-α、IL-1β和NE可以诱导肺成纤维细胞产生大量MMP_(2),参与肺泡基质的降解损伤和致纤维化过程,IL-6不诱导MMP_(2)产生,它可能通过诱导IL-1β和TNF-α的生成起作用。Objective:To investigate the correlation between inflammatory cytokines and matrix metalloproteinases(MMPs)during lung injury and pulmonary fibrosis.Methods:The three-dimensional culture model of human pulmonary mircovascular endothelia cells(HPMEC)/Human fetal lung fibroblasts(HFL)+typeⅠcollagen was established.The activity of MMP_(2) was detected by gelatin enzyme assay with different cytokine stimulation.The secretion of MMP_(2) by lung cells and the interaction between various cytokines and MMP_(2),as well as among various cytokines were observed.Results:HFL was the main cells producing MMP_(2),they produced more MMP_(2) when stimulated by IL-1β,TNF-αand neutrophil elastase(NE).However,IL-6 could not induce HFL to produce MMP_(2).HPMEC can only produce a very small amount of MMP_(2),and various cytokines can not induce HPMEC to produce more MMP_(2).In three-dimensional culture of HFL and HPMEC,TNF-α,IL-1βand NE can induce more MMP_(2).Conclusion:Inflammatory cytokines TNF-α,IL-1βand NE can induce lung fibroblasts to produce a large amount of MMP_(2),which is involved in the degradation and damage of alveolar matrix and fibrosis.IL-6 does not induce the production of MMP_(2),but it may act by inducing the production of IL-1βand TNF-α.

关 键 词：急性肺损伤 细胞因子风暴 基质金属蛋白酶 三维立体培养 肺成纤维细胞 肺微血管内皮细胞 

分 类 号：R562[医药卫生—呼吸系统]