Effect of Long-Term Inhalation of Toner on Extracellular Matrix in the Lungs of Rats In Vivo
Effect of Long-Term Inhalation of Toner on Extracellular Matrix in the Lungs of Rats In Vivo
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DOI：
10.1080/08958370590904517
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发表时间：
2005-01
影响因子：
2.1
通讯作者：
Dr. Yasuo Marimoto;Heungnam Kim;T. Oyabu;M. Hirohashi;H. Nagatomo;A. Ogami;H. Yamato;T. Higashi;I. Tanaka;T. Kasai
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文献类型：
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作者：
Dr. Yasuo Marimoto;Heungnam Kim;T. Oyabu;M. Hirohashi;H. Nagatomo;A. Ogami;H. Yamato;T. Higashi;I. Tanaka;T. Kasai
本研究采用大鼠模型，观察长期吸入墨粉对胶原细胞外基质合成和降解的病理变化及基因表达的影响。将雌性Wistar大鼠（10周龄）平均分为高浓度暴露组（H：15.2 mg/m3）、低浓度暴露组（L：5.5 mg/m3）和对照组。墨粉的质量中值空气动力学直径为4.5 μm。在1年或2年吸入期结束时处死大鼠。从左肺进行病理检查，并从右肺提取的mRNA的转录水平进行了半定量逆转录聚合酶链聚合酶（RT-PCR）评估。病理结果显示，20%（L，1年），40%（H，1年），56%（L，2年）和62%（H，2年）的轻度肺纤维化，而在任何接触组中均未观察到肺癌。在1年高浓度组中，大鼠肺中基质金属蛋白酶-2（MMP-2）和I型胶原mRNA的基因表达增加，而金属蛋白酶组织抑制剂-2（TIMP-2）的基因表达减少。2年高浓度组I型胶原和TIMP-2的mRNA水平升高，但MMP-2的mRNA水平未升高。这些数据表明，MMP，TIMP和胶原蛋白的基因表达的结果，在2年的曝光可能会导致胶原蛋白的积累相比，1年的曝光，和MMPs，TIMP和细胞外基质的表达失衡可能与墨粉诱导的肺纤维化。
We assessed the effects of long-term inhalation of toner on the pathological changes and gene expression with the synthesis and degradation of collagenous extracellular matrix in a rat model. Female Wistar rats (10 wk old) were divided evenly into a high concentration exposure group (H: 15.2 mg/m3), a low concentration exposure group (L: 5.5 mg/m3), and a control group. The mass median aerodynamic diameter of toner was 4.5 μm. The rats were sacrificed at the termination of a 1-yr or 2-yr inhalation period. Pathological examination was performed from the left lung, and transcriptional levels of mRNA extracted from the right lung were assessed by semiquantitative reverse-transcription polymerase chain polymerase (RT-PCR). The pathological findings showed mild pulmonary fibrosis in 20% (L, 1 yr), 40% (H, 1 yr), 56% (L, 2 yr) and 62% (H, 2 yr), while lung cancer was not observed in any of the exposed groups. In the 1-yr high-concentration group, gene expression of matrix metalloproteinase-2 (MMP-2) and type I collagen mRNA in the rat lungs increased, while tissue inhibitors of metalloproteinase-2 (TIMP-2) decreased. The 2-yr high-concentration group increased in message level of type I collagen and TIMP-2 but not that of MMP-2. These data suggested that results of gene expression of MMP, TIMP, and collagen in the 2-yr exposure may lead to accumulation of collagen compared to the 1-yr exposure, and that the imbalance of the expression of MMPs, TIMPs, and extracellular matrix might be associated with pulmonary fibrosis induced by toner.