Effects of silica on lung collagen.
Effects of silica on lung collagen.
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二氧化硅对肺胶原蛋白的影响。
DOI：
10.1002/9780470513323.ch11
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Reiser,KM
中科院分区：
文献类型：
--
作者：
Last,JA;Reiser,KM
向大鼠单次气管内注射50 mg结晶二氧化硅（石英）会产生硅肺。该动物模型可用于研究肺损伤早期、中期和晚期的胶原代谢，分别对应于肺损伤、离散肉芽肿的发展和成熟硅肺结节的发展阶段。早期阶段的特征在于肺胶原蛋白合成速率的快速增加（滴注一周内）和过量肺胶原蛋白沉积的增加（滴注两周内显著增加）。后期阶段的特征是在滴注后至少一年内过量肺胶原沉积持续增加。二氧化硅诱导的纤维化在迄今为止检查的所有动物模型（以及大多数人类纤维化疾病）中是独特的，因为沉积在肺中的过量胶原蛋白含有肺的两种主要胶原蛋白类型的正常比例：I型和III型。然而，这种胶原蛋白在生物化学上不同于正常的肺胶原蛋白。注射二氧化硅的大鼠肺中胶原蛋白的分子间交联存在可重现的特征性差异。在二氧化硅滴注的一个月内（迄今为止检查的最早时间点），可以观察到胶原蛋白的羟赖氨酸含量增加。可还原的双官能交联也更可能来源于羟基赖氨酸（即二羟基化与单羟基化交联的比率增加）。在二氧化硅滴注的四个月内（以及此后的逐渐增加），也可以观察到成熟的三功能交联羟基吡啶鎓（衍生自羟基赖氨酸的三个残基）的量增加，似乎与这些肺中成熟硅肺结节的演变平行。肺胶原交联的这些变化似乎是所有检查的肺纤维化动物模型所共有的，并且也与人纤维化肺中发生的变化一致。初步观察结果表明，交联位点保持不变：羟赖氨酸取代特定胶原α链一级结构中的赖氨酸，形成改变的交联。因此，可能存在病变肺纤维化胶原的分子标志物。
A single intratracheal injection of 50 mg crystalline silica (quartz) into rats produces silicosis. This animal model may be used to study collagen metabolism during the early, middle, and late phases of lung injury, corresponding respectively to the stages of lung injury, development of discrete granulomas, and development of mature silicotic nodules. The early phase is characterized by a rapid increase in the rate of synthesis of lung collagen (within one week of instillation) and increased deposition of excess lung collagen (significant increases within two weeks of instillation). Later phases are characterized by a continuing increase in deposition of excess lung collagen for at least one year after instillation. Silica‐induced fibrosis is unique among all the animal models (and in most human fibrotic diseases) thus far examined, in that the excess collagen deposited in the lung contains normal ratios of the two major collagen types of the lung: types I and III. This collagen is nonetheless biochemically different from normal lung collagen. There are reproducible and characteristic differences in the intermolecular cross‐links of the collagen in lungs from rats injected with silica. Within one month of silica instillation (the earliest time point examined thus far), an increased hydroxylysine content of collagen can be appreciated. The reducible difunctional cross‐links are also more likely to be derived from hydroxylysine (i.e. the ratio of dihydroxylated to monohydroxylated cross‐links increases). Within four months of silica instillation (and increasingly thereafter), increased amounts of the mature trifunctional cross‐link hydroxypyridinium (derived from three residues of hydroxylysine) can also be appreciated, seemingly paralleling the evolution of mature silicotic nodules in these lungs. These changes in cross‐linking of lung collagen seem to be common to all the animal models of pulmonary fibrosis examined, and are also consistent with changes occurring in human fibrotic lungs. Preliminary observations suggest that the locus of cross‐linking remains the same: hydroxylysine replaces lysine in the primary structure of a specific collagen α chain to form the altered cross‐links. Thus, there may be molecular markers for the collagen of fibrosis in diseased lungs.
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影响因子：
2.1
作者：
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影响因子：
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作者：
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影响因子：
8.3
作者：
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通讯作者：
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影响因子：
8.3
作者：
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通讯作者：
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影响因子：
6
作者：
J. Dauber;M. Rossman;G. Pietra;S. Jimenez;R. Daniele
通讯作者：
R. Daniele