Gene expression of cytokines and growth factors in the lungs after paraquat administration in mice
Gene expression of cytokines and growth factors in the lungs after paraquat administration in mice
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DOI：
10.1016/j.legalmed.2005.08.010
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发表时间：
2006-03-01
期刊：
影响因子：
1.5
通讯作者：
Kondo, Toshikazu
中科院分区：
文献类型：
--
作者：
Ishida, Yuko;Takayasu, Tatsunori;Kondo, Toshikazu
众所周知，摄入除草剂百草枯 (PQ) 会导致慢性期严重肺损伤。我们检查了 PQ 给药后细胞因子和生长因子的肺内基因表达。为了诱导肺损伤，C57BL/6 小鼠每周腹腔注射两次 20 mg/kg 的 PQ。组织病理学上，早期肺泡腔内大量水肿液。 PQ 攻击后 3 周，发现肺泡壁明显增厚，巨噬细胞和 T 细胞积聚。氮赞染色显示胶原蛋白积聚呈斑片状分布，表明肺纤维化。一致地，与对照组相比，肺内羟脯氨酸含量显着升高。半定量RT-PCR分析表明，与对照组相比，PQ攻击后3周肿瘤坏死因子-α和单核细胞趋化蛋白-1的基因表达显着增加。 PQ治疗后1周和2周时巨噬细胞炎症蛋白（MIP）-1α和MIP-2的mRNA表达分别显着增强。此外，PQ 治疗后的小鼠在 PQ 攻击后 2 周和/或 3 周表现出纤维生长因子基因表达增强，例如转化生长因子-β、血小板衍生生长因子-A、酸性成纤维细胞生长因子和肝细胞生长因子。据推测，这些分子的协同作用会因 PQ 攻击而导致肺纤维化。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
It is well known that the intake of paraquat (PQ), an herbicide, causes severe lung injury at chronic phases. We examined the intrapulmonary gene expression of cytokines and growth factors after PQ administration. To induce lung injury, C57BL/6 mice were intraperitoneally injected twice a week with 20 mg/kg of PQ. Histopathologically, at the early phase, lots of alveolar spaces contained edematous fluid. At 3 weeks after PQ challenge, a marked thickening of the alveolar walls with the accumulation of macrophages and T cells was found. Azan staining revealed the patchy distribution of collagen accumulation, indicating pulmonary fibrosis. Consistently, intrapulmonary hydroxyproline contents were significantly elevated, compared with the controls. Semi-quantitative RT-PCR analysis demonstrated that the gene expression of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 were significantly increased at 3 weeks after PQ challenge compared with the controls. The mRNA expression of macrophage inflammatory protein (MIP)-1 alpha and MIP-2 was significantly enhanced at I and 2 weeks after PQ treatment, respectively. Moreover, PQ-treated mice showed enhanced gene expression of fibrogenic growth factors such as transforming growth factor-beta, platelet-derived growth factor-A, acidic fibroblast growth factor, and hepatoctyte growth factor at 2 and/or 3 weeks after PQ challenge. The synergistic effects of these molecules are presumed to cause pulmonary fibrosis due to PQ challenge. (c) 2005 Elsevier Ireland Ltd. All rights reserved.