[二氧化硅暴露大鼠支气管肺泡灌洗液中细胞因子的变化]

Zhang Wei, Wang Rui, Wang Xin, Zhou Xiao-bao, Wang Hui, Zhang Hai-dong, Liu Zheng-liang

Shandong Academy of Occupational Health and Occupational Medicine, Jinan 250062, China.

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Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2013 Nov;31(11):801-5.

OBJECTIVE

To investigate the changes in the levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) in rats exposed to silica dust.

METHODS

Experimental rats were randomly divided into control group and three experimental groups (doses of dust: 15, 30, and 60 mg/ml), with 42 rats in each group. Each rat in the control group was treated with 1 ml of normal saline by intratracheal instillation, while each rat in the experimental groups was exposed to 1 ml of silica suspension by a single intratracheal instillation. Seven rats in each group were killed at 1, 3, 7, 14, 21, and 28 days after exposure, and then BALF was collected. Enzyme-linked immunosorbent assay was used to measure the levels of interleukin (IL)-1, IL-6, IL-16, macrophage inflammatory protein-1 alpha (MIP-1α), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β).

RESULTS

The levels of cytokines in each experimental group were higher than those in the control group at any time point. In the early stage of exposure (day 1-3), BALF IL-1 level increased significantly with the increase in dust dose, and on day 14, BALF IL-6 and IL-16 levels increased significantly with the increase in dust dose; the levels of IL-1, IL-6, and IL-16 in the experimental groups reached the peak on day 14. There were significant differences in the levels of MIP-1α and MCP-1 between the experimental groups (FMIP-1α = 30.106, P<0.01; FMCP-1 = 17.193, P<0.01). In each group, the level of MCP-1 varied significantly at different time points (F = 0.618, P>0.05). On day 1-14, BALF TNF-α level increased with the increase in dust dose, with a significant dose-response relationship (P < 0.05). In each experimental group, TNF-α level reached the peak on day 14. On days 14, 21, and 28, the high-dose group had significantly higher BALF TGF-β levels than the low-dose group (P<0.05); on days 14 and 28, the high-dose group had significantly higher BALF TGF-β levels than the middle-dose group (P<0.05).

CONCLUSION

IL-1, IL-6, IL-16, MIP-1α, MCP-1, and TNF-α play a role in the development and progression of silicosis inflammation. TGF-β may be related to (related to; associated with; correlated with) fibrosis.

目的

探讨二氧化硅粉尘暴露大鼠支气管肺泡灌洗液（BALF）中炎症细胞因子水平的变化。

方法

将实验大鼠随机分为对照组和三个实验组（粉尘剂量：15、30和60mg/ml），每组42只。对照组每只大鼠经气管内滴注1ml生理盐水，而实验组每只大鼠经气管内单次滴注1ml二氧化硅悬浮液。每组7只大鼠在暴露后1、3、7、14、21和28天处死，然后收集BALF。采用酶联免疫吸附测定法检测白细胞介素（IL）-1、IL-6、IL-16、巨噬细胞炎性蛋白-1α（MIP-1α）、单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子-α（TNF-α）和转化生长因子-β（TGF-β）的水平。

结果

各实验组细胞因子水平在任何时间点均高于对照组。在暴露早期（第1 - 3天），BALF中IL-1水平随粉尘剂量增加而显著升高，在第14天，BALF中IL-6和IL-16水平随粉尘剂量增加而显著升高；实验组中IL-1、IL-6和IL-16水平在第14天达到峰值。实验组之间MIP-1α和MCP-1水平存在显著差异（FMIP-1α = 30.106，P<0.01；FMCP-1 = 17.193，P<0.01）。每组中，MCP-1水平在不同时间点差异显著（F = 0.618，P>0.05）。在第1 - 14天，BALF中TNF-α水平随粉尘剂量增加而升高，存在显著的剂量反应关系（P < 0.05）。各实验组中，TNF-α水平在第14天达到峰值。在第14、21和28天，高剂量组BALF中TGF-β水平显著高于低剂量组（P<0.05）；在第14和28天，高剂量组BALF中TGF-β水平显著高于中剂量组（P<0.05）。