Chang X H, Zhu A, Liu F F, Zou L Y, Su L, Liu S K, Zhou H H, Sun Y Y, Han A J, Sun Y F, Li S, Li J, Sun Y B
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
2 Lanzhou Municipal Center for Disease Control, Lanzhou, China.
Hum Exp Toxicol. 2017 Aug;36(8):802-812. doi: 10.1177/0960327116666650. Epub 2016 Sep 5.
Nano nickel oxide (NiO), widely used in industry, has recently been discovered to have pulmonary toxicity. However, no subchronic exposure studies about nano NiO-induced pulmonary fibrosis have been reported. The objective of this study was to investigate pulmonary fibrosis induced by nano NiO and its potential mechanism in rats. Male Wistar rats ( n = 40, 200-240 g) were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg/kg), and micro NiO group (0.024 mg/kg). All rats were killed to collect lung tissue after intratracheal instillation of NiO particles twice a week for 6 weeks. To identify pulmonary fibrosis, Masson trichrome staining, hydroxyproline content, and collagen protein expression were performed. The results showed widespread lung fibrotic injury in histological examination and increased content of hydroxyproline, collagen types I and III in rat lung tissue exposed to nano NiO. To explore the potential pulmonary fibrosis mechanism, transforming growth factor beta 1 (TGF- β1) content was measured by enzyme-linked immunosorbent assay, and the messenger RNA expression of key indicators was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The TGF- β1 content was increased in nano NiO exposure groups, as well as the upregulated gene expression of TGF- β1, Smad2, Smad4, matrix metalloproteinase, and tissue inhibitor of metalloproteinase. The findings indicated that nano NiO could induce pulmonary fibrosis, which may be related to TGF- β1 activation.
纳米氧化镍（NiO）在工业中广泛应用，最近被发现具有肺毒性。然而，尚未有关于纳米NiO诱导肺纤维化的亚慢性暴露研究报道。本研究的目的是探讨纳米NiO诱导大鼠肺纤维化及其潜在机制。将雄性Wistar大鼠（n = 40，体重200 - 240 g）随机分为对照组、纳米NiO组（0.015、0.06和0.24 mg/kg）和微米NiO组（0.024 mg/kg）。所有大鼠每周经气管内滴注NiO颗粒两次，持续6周后处死以收集肺组织。为鉴定肺纤维化，进行了Masson三色染色、羟脯氨酸含量测定及胶原蛋白表达检测。结果显示，组织学检查发现纳米NiO暴露大鼠肺组织出现广泛的纤维化损伤，且肺组织中羟脯氨酸、I型和III型胶原蛋白含量增加。为探究潜在的肺纤维化机制，采用酶联免疫吸附测定法检测转化生长因子β1（TGF-β1）含量，并通过逆转录-定量聚合酶链反应（RT-qPCR）检测关键指标的信使核糖核酸表达。纳米NiO暴露组中TGF-β1含量增加，同时TGF-β1、Smad2、Smad4、基质金属蛋白酶和金属蛋白酶组织抑制剂的基因表达上调。研究结果表明，纳米NiO可诱导肺纤维化，这可能与TGF-β1激活有关。
