低氧时肾上腺髓质素对人胚肺成纤维细胞胶原合成和转化生长因子β_1表达的影响  

The Effects of Adrenomedullin on Collagen Synthesis and Transforming Growth Factor β_1 Production of Human Embryonic Lung Fibroblasts in Hypoxia

作　　者：郝淑玲[1] 于忠和[1] 齐保申[2] 罗继征[1] 周晓梅[2] 

机构地区：[1]北京军区总医院呼吸内科,北京100700 [2]中国医学科学院基础医学研究所生理室,北京100005

出　　处：《细胞生物学杂志》2004年第6期613-616,共4页Chinese Journal of Cell Biology

基　　金：国家自然科学基金资助项目(No.30070336)

摘　　要：观察低氧(2%O2)条件下肾上腺髓质素(ADM)对人胚肺成纤维细胞胶原合成和转化生长因子β1(TGF-β1)表达的影响。体外培养人胚肺成纤维细胞,分常氧和低氧24、48、72 h组,用[3H]-脯氨酸掺入法反映细胞总胶原合成和分泌,ELISA法检测细胞土清液中TGF-β1活化蛋白质含量。低氧24、48、72 h,细胞总胶原合成和分泌分别是常氧组的125.88%和124.74%、183.44% 和165.73%、152.55%和172.93%(P<0.01)。低氧24、72 h,ADM(10-7 mol/L)组细胞胶原合成分泌减少了19.24%和20.76%(P<0.01)、9.57%(P<0.05)和10.98%(P<0.01);低氧48 h,ADM(10-9、10-8、10-7mol/L)组胶原合成分泌分别降低了5.57%(P<0.05)和9.19%(P>0.05)、11.09%(P<0.01)和14.49%(P<0.05)、35.41%(P<0.01)和18.57%(P<0.05)。低氧48 h,细胞培养液中TGF-β1上升了24.17%(P<0.05),加入ADM(10-7mol/L),TGF-β1比对照组下降了17.53%(P<0.05);低氧72 h, ADM(10-7mol/L)组TGF-β1下降了19.49%(P<0.05)。低氧时ADM通过阻碍戍纤维细胞胶原合成而影响低氧性肺血管改建及损伤组织修复过程,ADM与TGF-β1可能通过相互拮抗,共同调节成纤维细胞胶原的生成。To determine the effects of adrenomedullin (ADM), a vasrelaxant peptide on the collagen synthesis and transforming growth factor β1 (TGF-β1) production of human embryonic lung fibroblasts in hypoxia. Human embryonic lung fibroblasts were cultured by outgrowth in vitro. Cells were exposed to hypoxia (2%O2) or normoxia after added ADM 10-9, 10-8, 10-7mol/L. Total collagen synthesis and secretion were detected by [3H]-proline incorporation. TGF-β1 production in culture supernatant were measured by ELISA. Compared to normoxia, hypoxia increased fibroblasts collagen synthesis and secretion and TGF-β1 production. When exposed to hypoxia for 24 h and 72 h, collagen synthesis and secretion in ADM(10-7mol/L) group were decreased by 19.24% and 20.76%(P<0.01), 9.57%(P<0.05) and 10.98%(P<0.01). Hypoxia for 48 h, collagen synthesis were inhibited by ADM(10-9,10-8 and 10-7mol/L) of 5.57%(P<0.05) and 9.19%(P>0.05),11.09%(P<0.01) and 14.49%(P<0.05), 35.41% (P<0.01) and 18.57%(P<0.05) respectively, in a dose-dependent manner. Hypoxia for 48 h and 72 h, TGF-β1 production were suppressed by 17.53% and 19.49% in ADM(10-7mol/L) group (P<0.05). In hypoxia, ADM influence the process of pulmonary vascular remodeling and wound healing by inhibiting collagen synthesis of fibroblasts. ADM may be a antagonistic substance of TGF-β1.

关 键 词：肾上腺髓质素 人胚肺成纤维细胞 胶原合成 转化生长因子β1 低氧性肺动脉高压 低氧环境 

分 类 号：R363[医药卫生—病理学]