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Title: [Expression and significance of NLRP3/IL-1β/TGF-β(1) signal axis in rat model of silicosis pulmonary fibrosis].
Author: Song ZS, Shao H, Chen YQ, Zhang R.
Journal: Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi; 2018 Nov 20; 36(11):819-823. PubMed ID: 30646643.
Abstract:
Objective: To investigate the expression and significance of NLRP3/IL-1β/TGF-β(1) signal axis in a rat model of silicosis and pulmonary fibrosis. Methods: Eighty healthy Wistar male rats of SPF grade were randomly divided into 4 groups: high (100 mg/ml) , medium (50 mg/ml) , low (25 mg/ml) concentration SiO(2) dusting group and normal negative control. Group, 20 in each group. Five rats were sacrificed at 7 d, 14 d, 28 d and 56 d after SiO(2) dusting. The degree of alveolitis and the degree of pulmonary fibrosis were observed. The enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1β in lung tissue. The expressions of NLRP3 and Caspase-1 in lung tissue of rats were detected by Western Blot. Results: The alveolitis score and fibrosis degree of the rats in the dust-receiving group were significantly higher than those in the control group at 7 d, 14 d, 28 d and 56 d, and the difference was statistically significant (P<0.01) . The concentrations of IL-1β, IL-18 and TGF-β1 in 14 d, 28 d and 56 d were significantly higher than those in the control group (P<0.01) . The expressions of NLRP3 and Caspase-1 in lung tissue of rats exposed to dust were 7 d and 14 d, 28 d, 56d were higher than the control group (P<0.01) ; the expression levels of NLRP3, Caspase-1, IL-1β, IL-18 and TGF-β(1) in the low, medium and high concentration SiO(2) dusting group were 7 d, 14 d and The difference between the two groups was statistically significant (P<0.05) , and both showed a time-effect relationship with the increase of dusting time. Conclusion: NLRP3 and its downstream factors Caspase-1, IL-1β, IL-18 and TGF-β1 are highly expressed in the lung tissue of rats with silicosis and pulmonary fibrosis, suggesting that the NLRP3/IL-1β/TGF-β(1) signal axis may be associated with silicosis. Pulmonary fibrosis has a close relationship and plays a role in the formation of silicosis. 目的： 探讨NLRP3/IL-1β/TGF-β(1)信号轴在矽肺肺纤维化大鼠模型中的表达情况及意义。 方法： 选择健康SPF级Wistar雄性大鼠80只，随机分为4组，分别为高（100 mg/ml）、中（50 mg/ml）、低（25 mg/ml）浓度SiO(2)染尘组和正常对照组，每组20只。各组分别在SiO(2)染尘后7 d、14 d、28 d、56 d处死5只大鼠，观察肺组织肺泡炎程度及肺纤维化程度，采用酶联免疫吸附试验（ELISA）检测肺组织中IL-1β、IL-18、TGF-β(1)含量，Western Blot法检测大鼠肺组织中NLRP3、Caspase-1蛋白表达情况。 结果： 与正常对照组比较，各染尘组大鼠7 d、14 d、28 d、56 d的肺泡炎评分、纤维化程度明显升高，差异均有统计学意义（P<0.01）；与正常对照组比较，各染尘组大鼠7 d、14 d、28 d、56 d的IL-1β、IL-18、TGF-β(1)浓度明显升高（P<0.01）；与正常对照组比较，各染尘组大鼠肺组织中NLRP3、Caspase-1蛋白表达在7 d、14 d、28 d、56 d均升高（P<0.01）；低、中、高浓度SiO(2)染尘组内NLRP3、Caspase-1、IL-1β、IL-18和TGF-β(1)表达量在7 d、14 d和28 d间两两比较，差异均有统计学意义（P<0. 05），均呈随着染尘时间的增加而升高的时间-效应关系。 结论： NLRP3及其下游因子Caspase-1、IL-1β、IL-18、TGF-β(1)在矽肺肺纤维化大鼠模型肺组织中高表达，提示NLRP3/IL-1β/TGF-β(1)信号轴可能与矽肺肺纤维化有密切的关系，在矽肺形成过程中发挥了作用。.

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