Nano-ITO induce pulmonary alveolar proteinosis through oxidative stress and activation of NF-κB/Nrf2 signaling pathway
10.3760/cma.j.cn121094-20240313-00094
- VernacularTitle:氧化铟锡纳米颗粒通过氧化应激激活NF-κB/Nrf2通路诱导大鼠肺泡蛋白沉积症
- Author:
Yinqiao LIN
1
;
Yi ZHANG
;
Xiaoyang CHEN
;
Weikang LI
;
Yujing NIU
;
Xuefei WANG
;
Nan LIU
;
Gai LI
Author Information
1. 华北理工大学公共卫生学院研究院，河北省煤矿卫生与安全重点实验室，唐山 063210
- Publication Type:Journal Article
- Keywords:
Metal nanoparticles;
Rats;
Pulmonary alveolar proteinosis;
Indium-tin oxide nanoparticles;
Oxidative stress;
Inflammatory response;
NF-κB/Nrf2 pathway
- From:
Chinese Journal of Industrial Hygiene and Occupational Diseases
2025;43(2):81-90
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of the nuclear factor-kappa B (NF-κB) /nuclear factor E2 related factor 2 (Nrf2) pathway in the occurrence of lung tissue in the pulmonary alveolar proteinosis (PAP) model of rats induced by indium tin oxide nanoprticles (Nano-ITO) .Methods:In October 2019, 120 SD rats were divided into 3, 7, 14, 28, 56, and 84 day Nano ITO exposure groups and corresponding time point control groups, with 10 rats in each group; the exposure group was treated with 6 mg/kg·bw Nano-ITO via non exposed tracheal injection, twice a week. Time-course studies were performed to examine the pulmonary toxicity induced by Nano-ITO. At the end of the experiment, cytokines levels and oxidative stress were analyzed in the bronchoalveolar lavaged fluid (BALF). Rat lung tissues were also harvested for staining with HE, PAS, Masson, and Oil Red O. Ultrastructure of lung tissue cells was observed by transmission electron microscope. The localization and expression of NF-κB p65, IκB-α, IKK-β, Nrf2, NQO1, HO-1 were observed by immunohistochemistry, Western blot and real-time fluorescent quantitative PCR. The comparison between the two groups was analyzed by independent sample T test, and the comparison between the multiple groups was analyzed by one-way ANOVA.Results:Nano-ITO intratracheal instillation caused pulmonary toxicity by inducing acute inflammation, granuloma (nodule) formation, and alveolar proteinosis. ELISA analysis showed that, compared with the corresponding time points control groups, the levels of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), malondialdehyde (MDA), interleukin (IL) -1β, IL-6, tumor necrosis factor alpha (TNF-α), IL-10, total protein (TP), and lactate dehydrogenase (LDH) in BALF of rats exposed to Nano ITO were all increased ( P<0.05) ; The protein expression of Nrf2 and NF-κB p65 was upregulated in rat lung tissue, while the protein expression of KK-β was increased ( P<0.01). Nrf2 and its downstream proteins NQO1 and HO-1 were highly expressed in Nano-ITO-induced PAP rat. Conclusion:NF-κB/Nrf2 signal pathway is involved in the process of Nano-ITO induced pulmonary alveolar proteinosis in rats.
