Dolhnikoff M, Mauad T, Ludwig M S
Meakins Christie Laboratories, Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Québec, Canada.
Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1750-7. doi: 10.1164/ajrccm.160.5.9812040.
We investigated in vivo and in vitro oscillatory mechanics in bleomycin-induced fibrotic lungs and correlated these with morphometric changes in the collagen-elastin matrix and contractile cells. Fischer rats received bleomycin sulfate (BLEO,1.5 U) or saline intratracheally. Four weeks later tracheal flow and tracheal and alveolar pressure (using alveolar capsules) were measured in open-chested rats during mechanical ventilation (V T = 8 ml/kg, f = 1 Hz, PEEP = 4 cm H(2)O). Total lung, tissue, and airway resistance (R) and lung elastance (E) were calculated. In addition, excised parenchymal strips (10 x 2 x 2 mm) were studied in the organ bath. Strips were attached to a force transducer at one end and to a servo-controlled lever arm that effected length (L) changes at the other. Sinusoidal oscillations were applied (f = 1 Hz, amplitude = 2. 5% resting L and tension = 0.7 g) and R, E, and hysteresivity (eta) were calculated. Strips were then exposed to acetylcholine (ACh, 10(-)(3) M). The amount of collagen and elastic fibers in the parenchymal strip was assessed semiquantitatively by point-counting in 5-micrometer-thick sections stained with either Sirius Red or Weigert's Resorcin-fuchsin. alpha-Smooth-muscle-specific actin was detected immunohistochemically. Both in vivo and in vitro, R, E, and eta were significantly increased in BLEO rats (p < 0.05). The % increase in R, E and eta after Ach was greater in BLEO rats (p < 0. 01). There was also a significant increase in the volume proportion of collagen, elastic fibers, and actin in the parenchyma (p < 0.01). In BLEO rats, baseline R and E were correlated with the volume proportion of collagen in the parenchyma. We conclude that changes in the collagen-elastin matrix contribute to changes in the viscoelastic properties of bleomycin-treated rat lungs. Dolhnikoff M, Mauad T, Ludwig MS. Extracellular matrix and oscillatory mechanics of rat lung parenchyma in bleomycin-induced fibrosis.
我们研究了博来霉素诱导的纤维化肺组织的体内和体外振荡力学，并将其与胶原 - 弹性蛋白基质和收缩细胞的形态计量学变化相关联。Fischer大鼠经气管内给予硫酸博来霉素（BLEO，1.5 U）或生理盐水。四周后，在机械通气（VT = 8 ml/kg，f = 1 Hz，PEEP = 4 cm H₂O）期间，对开胸大鼠测量气管流量、气管和肺泡压力（使用肺泡囊）。计算全肺、组织和气道阻力（R）以及肺弹性（E）。此外，在器官浴中研究切除的实质条带（10×2×2 mm）。条带一端连接到力传感器，另一端连接到可实现长度（L）变化的伺服控制杠杆臂。施加正弦振荡（f = 1 Hz，振幅 = 2. 5%静息L，张力 = 0.7 g）并计算R、E和滞后率（η）。然后将条带暴露于乙酰胆碱（ACh，10⁻³ M）。通过对用天狼星红或魏格特间苯二酚品红染色的5微米厚切片进行点计数，半定量评估实质条带中胶原蛋白和弹性纤维的含量。免疫组织化学检测α - 平滑肌特异性肌动蛋白。在体内和体外，BLEO大鼠的R、E和η均显著增加（p < 0.05）。Ach作用后，BLEO大鼠的R、E和η的增加百分比更大（p < 0. 01）。实质中胶原蛋白、弹性纤维和肌动蛋白的体积比例也显著增加（p < 0.01）。在BLEO大鼠中，基线R和E与实质中胶原蛋白的体积比例相关。我们得出结论，胶原 - 弹性蛋白基质的变化导致博来霉素处理的大鼠肺组织粘弹性特性的改变。多尔尼科夫M，毛阿德T，路德维希MS。博来霉素诱导的纤维化大鼠肺实质的细胞外基质和振荡力学。
