基础医学与临床 ›› 2008, Vol. 28 ›› Issue (3): 232-237.

• 研究论文 • 上一篇    下一篇

TGF-β1诱导成肌纤维细胞形成在低氧性

李柏完 蒋永亮 戴爱国   

  1. 慢性阻塞性肺病 肺动脉高压 湖南省老年医院老年医学研究所呼吸疾病研究室
  • 收稿日期:2007-05-08 修回日期:2007-08-31 出版日期:2008-03-25 发布日期:2008-03-25
  • 通讯作者: 蒋永亮

Role of transforming growth factor-?1 tnducing myofibroblast formation in hypoxic pulmonary vascular remodeling

Bo-wan LI, Yong-liang JIANG, Ai-guo DAI   

  1. Department of Respiratory Internal Medicine; the Third Affiliated Hospital of Nanhua University
  • Received:2007-05-08 Revised:2007-08-31 Online:2008-03-25 Published:2008-03-25
  • Contact: Yong-liang JIANG,

摘要: 目的 探讨转化生长因子-β1(TGF-β1)诱导成肌纤维细胞形成在低氧性肺血管重塑中的作用。 方法 40只成年雄性Wistar大鼠随机分成:对照组、低氧3、7、14和21d组,每组8只,测大鼠平均肺动脉压(mPAP)、血管形态学指标、右室肥大指数(RVHI);免疫组化检测α-平滑肌肌动蛋白(α-SMA)的表达,原位杂交和免疫组化检测TGF-β1基因表达,透射电镜观察腺泡内血管壁细胞表型,细胞培养观察低氧和TGF-β1诱导人胚肺成纤维细胞是否发生表型转化。 结果 (1)低氧7d后大鼠mPAP升高 (P<0.05)。低氧14d后出现肺血管重塑、右心室肥大。(2)从低氧7d开始无肌型动脉、部分肌型动脉、肌型动脉的构成比分别是39%、46%和15% 与对照组60%、35%和5%比较差异显著(PX2<0.005)。(3)腺泡内肺动脉管壁α-SMA的表达随着低氧时间的延长逐渐增多。低氧14d TGF-β1 mRNA表达增高(P<0.01);TGF-β1蛋白在对照组呈弱阳性,低氧3d表达增强(P<0.01),低氧7d达高峰(P<0.01)。(4)透射电镜证实成肌纤维细胞含有特异性的微丝和丰富的粗面内质网。(5)细胞培养表明低氧能够刺激成纤维细胞发生表型转化,TGF-β1能够促进成纤维细胞表型转化的发生。 结论 转化生长因子β1诱导成肌纤维细胞形成是低氧性肺血管重塑的重要原因之一。

Abstract: Objective To investigate transforming growth factor-┈1(TGF-┈1) induces myofibroblast formation in hypoxic pulmonary vascular remodeling of rats. Methods Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21days. Mean pulmonary arterial pressure (mPAP), vessel morphometry, right ventricle hypertrophy index (RVHI) were measured. Immunocytochemistry were used to measure the expression of メ-smooth-muscle actin(メ-SMA) and TGF-┈1 in pulmonary artery walls, however, in situ hybridization were used to measure the expression of TGF-┈1 mRNA in pulmonary artery walls. Ultrastructural characteristics of cell phenotype in alveolar wall vessels were observed by electron microscopy. Cell culture observed human embryonic lung fibroblasts(KMB17) phenotype after induction of hypoxia and TGF-┈1. Results (1) mPAP increased significantly after 7-day of hypoxia[(18.41【0.37)mmHg,P<0.05]. Pulmonary artery remodeling index and right ventricle hypertrophy became evident after 14-day of hypoxia. (2) The distribution of nonmuscular, partially muscular, and muscular vessels(39%、46%、15% ) is significantly different (PX2<0.005= from hypoxia 7d than that in the control group (60%、35%、5% ).(3)The intra-acinar pulmonary arteries with cells expressing メ-SMA increased most with hypoxic time by immunocytochemistry. TGF-┈1 mRNA expression in pulmonary arterial walls was increased significantly after 14 days of hypoxia(0.385【0.028, P<0.01),but showed no obvious changes after 3 or 7 days of hypoxia. In pulmonary tunica adventitia and tunica media, TGF-┈1 staining was poorly positive in control rats, but was markedly enhanced after 3 days of hypoxia(0.198【0.031,P<0.01), reaching its peak after 7 days of hypoxia(0.267【0.035,P<0.01). (4) The myofibroblast phenotype was confirmed by electron microscopy, which revealed microfilaments and a well-developed rough endoplasmic reticulum.(5) Cell culture showed that hypoxia induced KMB17 phenotype transforming and TGF-モ1 accelerated its transforming.Conclusion It is reasonable to believe that transforming growth factor-┈1(TGF-┈1) induces myofibroblast formation are the important causes in hypoxic pulmonary vascular remodeling of rats.