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吸入不锈钢焊接粉尘及其可溶形式的大鼠中克拉拉细胞蛋白、催乳素以及蛋白质NF-κB和c-Jun/AP-1转录因子的水平

Clara cells protein, prolactin and transcription factors of protein NF-ĸB and c-Jun/AP-1 levels in rats inhaled to stainless steel welding dust and its soluble form.

作者信息

Hałatek Tadeusz, Stanisławska Magdalena, Świercz Radosław, Domeradzka-Gajda Katarzyna, Kuraś Renata, Wąsowicz Wojciech

机构信息

Nofer Institute of Occupational Medicine, Łódź, Poland (Department of Biological and Environmental Monitoring).

Nofer Institute of Occupational Medicine, Łódź, Poland (Department of Toxicology and Carcinogenesis).

出版信息

Int J Occup Med Environ Health. 2018 Oct 23;31(5):613-632. doi: 10.13075/ijomeh.1896.01234. Epub 2018 Oct 3.

DOI:10.13075/ijomeh.1896.01234
PMID:30283154
Abstract

OBJECTIVES

Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese, and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. Bronchiolar epithelium Clara cells/club cells, coordinate these inflammatory responses. Clara cells secretory protein (CC16) with ant-inflammatory role.

MATERIAL AND METHODS

The pulmonary toxicity of welding dust (WD) was assessed for Wistar rats exposed to 60 mg/m of respirable-size welding dust (mean diameter 1.17 μm for 1 and 2 weeks (6 h/day, 5 days/week)) or the aerosols of soluble form (SWD) in the nose-only exposure chambers. Additionally the effect of antiinflammatory betaine supplementation was assessed. Clara cells secretory protein, differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase - LDH) activities were determined in bronchoalveolar lavage fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) and prolactin concentrations were assessed in serum. Histopathology examination of lung, brain, liver, kidney, spleen was done. Additionally slices of brain and lung were exanimated in laser ablation inductively coupled plasma mass spectrometry.

RESULTS

Both WD and SWD exposure evoked large bronchiolar infiltration shoved in histopathology examination. In this study, TBARS inversely correlated with a significant decrease of CC16 concentration that occurred after instillation of both WD and SWD indicating decreased anti- inflammatory potential in the lung. In WD exposed rats prolactin correlated with nuclear factor-kappa B (NF-κB), LDH, TBARS and serum levels Cr, Ni and inversely with c-Jun. In SWD exposed rats prolactin correlated with CC16 indicated effect of prolactin on the population of epithelial cells.

CONCLUSIONS

In the current study, deleterious effects of repeated inhalation stainless steel welding dust form on club (Clara) cell secretory protein (CC16) were demonstrated. Clara cells secretory protein relation with prolactin in exposed rats to welding dust were shown and explored whether the NF-κB and c-Jun/activator protein 1 related pathway was involved. Int J Occup Med Environ Health 2018;31(5):613-632.

摘要

目的

在动物模型中,产生含有有毒金属烟雾(如六价铬(Cr(VI))、锰和镍(Ni))的焊接工艺与肺损伤、炎症及肺肿瘤促进有关。细支气管上皮的克拉拉细胞/俱乐部细胞协调这些炎症反应。克拉拉细胞分泌蛋白(CC16)具有抗炎作用。

材料与方法

在仅经鼻暴露舱中,对暴露于60mg/m³可吸入粒径焊接粉尘(平均直径1.17μm,持续1周和2周,每天6小时,每周5天)或可溶性形式气溶胶(SWD)的Wistar大鼠评估焊接粉尘(WD)的肺毒性。此外,评估了补充抗炎性甜菜碱的效果。在支气管肺泡灌洗液中测定克拉拉细胞分泌蛋白、细胞分类计数、总蛋白浓度和细胞酶(乳酸脱氢酶 - LDH)活性,并在血清中评估皮质酮、硫代巴比妥酸反应性物质(TBARS)和催乳素浓度。对肺、脑、肝、肾、脾进行组织病理学检查。此外,对脑和肺切片进行激光烧蚀电感耦合等离子体质谱分析。

结果

组织病理学检查显示,WD和SWD暴露均引起细支气管大量浸润。在本研究中,TBARS与WD和SWD滴注后CC16浓度的显著降低呈负相关,表明肺中的抗炎潜力降低。在暴露于WD的大鼠中,催乳素与核因子 - κB(NF - κB)、LDH、TBARS以及血清中Cr、Ni水平呈正相关,与c - Jun呈负相关。在暴露于SWD的大鼠中,催乳素与CC16相关,表明催乳素对上皮细胞群体有影响。

结论

在本研究中,证实了反复吸入不锈钢焊接粉尘对克拉拉细胞分泌蛋白(CC16)的有害影响。展示了暴露于焊接粉尘的大鼠中克拉拉细胞分泌蛋白与催乳素的关系,并探讨了是否涉及NF - κB和c - Jun/激活蛋白1相关途径。《国际职业医学与环境卫生杂志》2018年;31(5):613 - 632。

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