Effects of silica exposure on the cardiac and renal inflammatory and fibrotic response and the antagonistic role of interleukin-1 beta in C57BL/6 mice
Effects of silica exposure on the cardiac and renal inflammatory and fibrotic response and the antagonistic role of interleukin-1 beta in C57BL/6 mice
复制标题
二氧化硅暴露对C57BL/6小鼠心脏和肾脏炎症和纤维化反应的影响以及白细胞介素1β的拮抗作用
DOI：
10.1007/s00204-014-1405-5
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发表时间：
2016-02-01
影响因子：
6.1
通讯作者：
Chen, Weihong
中科院分区：
文献类型：
--
作者：
Guo, Jiali;Shi, Tingming;Chen, Weihong
目前的流行病学研究表明，结晶二氧化硅暴露与心血管和肾脏疾病的风险增加有关；然而，对心脏和肾脏的潜在病理损伤及其潜在机制尚未完全阐明。本研究旨在探讨二氧化硅诱导的心脏和肾脏的炎症和纤维化变化，并评估白细胞介素(IL)-1 β (β)在二氧化硅诱导的心脏和肾脏损伤中的作用。在本研究中，通过气管内灌注二氧化硅粉尘建立了小鼠二氧化硅暴露模型。用抗IL-1β单克隆抗体（mAb）中和肺泡和血清中的IL-1β。real-time PCR研究显示(1)吸入二氧化硅通过升高TNF-α、IL-6和MCP-1 mRNA水平诱导心脏和肾脏的炎症反应；(2)心肌早期纤维化反应表现为ⅰ型胶原和纤维连接蛋白mRNA水平升高。病理结果显示肾脏纤维化，TGF-β、ⅰ型胶原、ⅲ型胶原、纤维连接蛋白mRNA水平显著升高。进一步的研究表明，使用抗il -1β mAb可降低吸入二氧化硅引起的心脏和肾脏炎症反应，并减轻小鼠肾脏纤维化。综上所述，本研究发现吸入二氧化硅诱导小鼠心脏炎症和早期纤维化反应，小鼠肾脏炎症反应和纤维化。IL-1β的中和减轻了硅致心脏和肾脏的炎症反应，减少了小鼠肾脏的纤维化。
Current epidemiological studies suggest that crystalline silica exposure is associated with an increased risk of cardiovascular and renal disease; however, the potential pathological damage of the heart and kidney and its underlying mechanisms have not been completely elucidated. This study tried to investigate the silica-induced inflammatory and fibrotic changes in the heart and kidney and evaluate the role of interleukin (IL)-1 beta (β) in silica-induced cardiac and renal damage. In this study, a silica-exposed model was generated by intratracheally instilling silica dust in mice. The anti-IL-1β monoclonal antibody (mAb) was used to neutralise IL-1β in the pulmonary alveolus and serum. The real-time PCR studies showed that (1) inhalational silica induced inflammatory responses in the heart and kidney by elevated mRNA levels of TNF-α, IL-6 and MCP-1; (2) early fibrotic responses in the heart were observed as elevated mRNA levels of collagen I and fibronectin. What is more, fibrosis of the kidney was demonstrated by pathological results and significantly increased mRNA levels of TGF-β, collagen I, collagen III and fibronectin. Further studies showed that usage of anti-IL-1β mAb decreased the inflammatory response of the heart and kidney induced by inhalational silica and also attenuated fibrosis in the mouse kidney. In conclusion, this study found that inhaled silica induced inflammatory and early fibrotic responses in the mouse heart and inflammatory response and fibrosis in the mouse kidney. Neutralisation of IL-1β attenuated the silica-induced inflammatory response of the heart and kidney and decreased fibrosis in the mouse kidney.