Changes in extracellular matrix and tissue viscoelasticity in bleomycin-induced lung fibrosis - Temporal aspects
Changes in extracellular matrix and tissue viscoelasticity in bleomycin-induced lung fibrosis - Temporal aspects
复制标题
DOI：
10.1164/ajrccm.162.4.9912011
复制
发表时间：
2000-10-01
影响因子：
24.7
通讯作者：
Ludwig, MS
中科院分区：
文献类型：
--
作者：
Ebihara, T;Venkatesan, N;Ludwig, MS
博来霉素诱导的肺纤维化由于细胞外基质（ECM）的改变而导致组织机械性质的变化。振荡力学和基质的变化如何随时间演变还没有得到解决。向Sprague-Dawley大鼠气管内滴注硫酸博来霉素（BM）（1.5 U）;对照动物（C）接受盐水。在BM后第7、14和28天，获得实质条（7 x 2 x 2 mm），并将条悬浮在Krebs填充的器官浴中。该条的一端连接到力（F）传感器，另一端连接到实现正弦长度（L）振荡的杠杆臂。在2 kPa的操作应力下，以不同的振幅（静息L的1、3和10%）和频率（f = 0.3、1、3和10 Hz）振荡条带。通过将F和L的变化拟合到运动方程来估计阻力（R）和弹性（E）。滞后性（eta）计算为eta =（R/E）2 π f。然后将条带固定用于胶原蛋白、弹性纤维和小蛋白聚糖（PG）、双糖链蛋白聚糖和纤调蛋白（FM）的形态学研究。与C条相比，BM条的R和E显著更大，eta显著更小（p < 0.001）。R和E的增加在BM后14天达到峰值; eta的减少在第7天达到最大。BM肺条中双糖蛋白聚糖在所有时间点均增加，FM和弹性纤维在14和28 d增加，胶原仅在28 d增加。因此，在胶原蛋白含量增加之前，力学变化最大。此外，我们证明了biglycan和所有机械参数之间的显着相关性。这些数据表明，PG的变化可能是决定在该纤维化模型中肺组织粘弹性行为的变化的关键。
Bleomycin-induced lung fibrosis results in changes in tissue mechanical properties due to alterations in the extracellular matrix (ECM). How oscillatory mechanics and changes in the matrix evolve over time has not been addressed. Sprague-Dawley rats were instilled with bleomycin sulfate (BM) (1.5 U) intratracheally; control animals (C) received saline. At 7, 14 and 28 d after BM, parenchymal strips (7 x 2 x 2 mm) were obtained and strips suspended in a Krebs-filled organ bath. One end of the strip was attached to a force (F) transducer and the other to a lever arm that effected sinusoidal length (L) oscillations. Strips were oscillated at varying amplitudes (1, 3, and 10% of resting L) and frequencies (f = 0.3, 1, 3, and 10 Hz) at an operating stress of 2 kPa. Resistance (R) and elastance (E) were estimated by fitting changes in F and L to the equation of motion. Hysteresivity (eta) was calculated as eta = (R/E) 2 pi f. Strips were then fixed for morphological study of collagen, elastic fibers, and the small proteoglycans (PGs), biglycan and fibromodulin (FM). R and E were significantly greater and eta significantly less in BM versus C strips (p < 0.001). The increase in R and E peaked at 14 d after BM; the decrement in eta was maximal at Day 7. Biglycan was increased in BM lung strips at all time points, FM and elastic fibers were increased at 14 and 28 d, and collagen was increased at 28 d only. Hence, changes in mechanics were maximal before collagen content had increased. In addition, we demonstrated a significant correlation between biglycan and all mechanical parameters. These data suggest that changes in PGs may be critical in determining changes in lung tissue viscoelastic behavior in this fibrosis model.