Interventional effect of metformin on pulmonary inflammation and pulmonary fibrosis in silicotic rats
10.3760/cma.j.cn121094-20200930-00552
- VernacularTitle:二甲双胍对矽肺大鼠肺炎及肺纤维化的干预作用
- Author:
Shuxian LI
1
;
Xinru PANG
;
Haiyue YAN
;
Juan ZHANG
;
Qiang JIA
;
Chao LI
;
Hua SHAO
;
Gongchang YU
Author Information
1. 250062 济南，山东省职业卫生与职业病防治研究院，山东第一医科大学（山东省医学科学院）
- Keywords:
Silicosis;
Fibrosis;
Metformin;
Rats;
Inflammatory factors;
Epithelial-mesenchymal transition (EMT)
- From:
Chinese Journal of Industrial Hygiene and Occupational Diseases
2021;39(10):726-732
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the interventional effect of metformin on pulmonary inflammation and pulmonary fibrosis in silicotic rats.Methods:In April 2019, 48 Wistar male rats of SPF grade were randomly divided into negative control group, metformin control group, silicon dioxide (SiO 2) model group, low, medium and high dose metformin intervention group according to the random number table method, 8 rats in each group. The SiO 2 model group and the low, medium and high dose metformin intervention groups were given 1 ml 50 mg/ml of SiO 2 by intratracheal instillation, the negative control group and the metformin control group were given 1 ml normal saline by intratracheal instillation. 24 hours later, the low, medium and high dose metformin intervention groups and the metformin control group were treated with 100, 200, 400 and 400 mg/kg metformin daily, the control and SiO 2 model groups received normal saline daily. Then the rats were sacrificed at the 28th day after SiO 2 exposure. The changes of rat body weight and pathological examination of rat lung tissue were observed, and the lung organ coefficient, the content of hydroxyproline (HYP) , the expression levels of inflammatory factors transforming growth factor beta1 (TGF-β1) , tumor necrosis factor-alpha (TNF-α) , interleukin-1beta (IL-1β) and the protein expression of E-cadherin (E-Cad) , Vimentin, α-SMA were detected. Results:Compared with the negative control group, SiO 2 model group had a significant decrease in the body weight of rats ( P<0.05) , lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-β1, TNF-α, IL-1β were all significantly increased ( P<0.05) . Compared with the SiO 2 model group, the weights of the rats in the medium and high dose intervention group of metformin increased significantly ( P<0.05) . And after intervention with different doses of metformin, the lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-β1, TNF-α and IL-1β were significantly decreased ( P<0.05) . Immunohistochemistry and Western blotting results showed that compared with the negative control group, the expression of E-Cad of the SiO 2 model group was decreased, and the expression levels of Vimentin and α-SMA were significantly increased ( P<0.05) . After metformin intervention, the expression of E-Cad was significantly increased, the expression levels of Vimentin and α-SMA were significantly decreased ( P<0.05) . Conclusion:Metformin can reduce lung tissue inflammation and fibrosis in rats exposed to SiO 2 dust, which may be related to reducing the expression of inflammatory factors in lung tissue and inhibiting the EMT process.
