The effect of dust fine particles on TNF-α, MMP, TGF-β<sub>1</sub>, and collagens in the lung tissue of rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LI Yi ¹ ,  LEI Fengfeng ² , HOU Yinhuan ³ , SANG Yingzhu ²

1. Department of Respiration In Cadre Ward, The People’s Hospital of Gansu Province, Lanzhou, Gansu 730000, P. R. China;
2. Department of Respiratory Medicine, The People’s Hospital of Gansu Province, Lanzhou, Gansu 730000, P. R. China;
3. Department of Respiratory Medicine, Jingning County Hospital, Pingliang, Gansu 744000, P. R. China;

Corresponding author：

LEI Fengfeng, Email: syingzhu@126.com

Keywords：

Sandstorm; Tumor necrosis factor-α; Matrix metalloproteinase; Transforming growth factor-β₁; Pulmonary collagen

DOI：

10.7507/1671-6205.201910012

Video：

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Objective To investigate the effect of dust fine particles on tumor necrosis factor-α (TNF-α), matrix metalloproteinase (MMP), transforming growth factor-β₁ (TGF-β₁), and collagens in the lung tissue of rats.Methods According to random number table method, 96 male Wistar rats were divided into an untreated control group, a treated control group and an experimental group, with 32 rats in each group. The experimental group was exposed to the wind tunnel simulation of sandstorm (5 days per week, 5 hours per day); the untreated control group was put in the standard living environment next to the wind tunnel; the treated control group was exposed to the same wind tunnel simulation of sandstorm for 5 hours every day, the speed of wind was the same as the experimental group, but without dust; On the 30^th, 60^th, 90^th, and 120^th day, the levels of TNF-α, MMP-2, MMP-9, TGF-β₁, lung collagen type Ⅰ and Ⅲ in the lung tissue of rats were determined by enzyme linked immunosorbent assay.Results Compared with the untreated control group and the treated control group, the content of TNF-α was higher in the experimental group on 30th, 60^th, 90^th and 120^th day (all P<0.05). The contents of MMP-9 and MMP-2 in the experimental group on 60^th and 90^th day were significantly higher than those in the untreated group and the treated control group, respectively (all P<0.05). On the 30^th, 60^th, 90^th, and 120^th day, the content of TGF-β₁ in the experimental group was significantly higher compared with the two control groups (all P<0.05). The contents of lung collagen type Ⅰ and type Ⅲ were higher in the experimental group on 60^th, 90^th and 120^th day, respectively, compared with the two control groups (all P<0.05).Conclusions The strong sandstorm environmental exposure to a certain period of time can promote lung interstitial collagen deposition in rat. With the prolonged exposure time, the deposition of collagen increases. TNF-α, MMP-2, MMP-9 and TGF-β₁ may all participate and induce the process of pulmonary fibrosis.

Citation： LI Yi, LEI Fengfeng, HOU Yinhuan, SANG Yingzhu. The effect of dust fine particles on TNF-α, MMP, TGF-β₁, and collagens in the lung tissue of rats. Chinese Journal of Respiratory and Critical Care Medicine, 2020, 19(3): 264-269. doi: 10.7507/1671-6205.201910012 Copy

1.	刘新春, 钟玉婷, 何清, 等. 塔克拉玛干沙漠腹地沙尘暴过程大气颗粒物浓度及影响因素分析. 中国沙漠, 2011, 31(6): 1548-1553.
2.	Atkinson RW, Kang S, Anderson HR, et al. Epidemiological time series studies of PM2.5 and daily mortality and hospital admissions: a systematic review and meta-analysis. Thorax, 2014, 69(7): 660-665.
3.	Cao XJ, Lei FF, Liu H, et al. Effects of dust storm fine particle-inhalation on the respiratory, cardiovascular, endocrine, hematological, and digestive systems of rats. Chin Med J (Engl), 2018, 131(20): 2482-2485.
4.	雷丰丰, 党雅梅, 张长青. 沙尘暴对大鼠肺组织影响的病理学观察. 中华病理学杂志, 2015, 44(3): 199-201.
5.	雷丰丰, 王学斌, 刘华. 沙尘气溶胶暴露对大鼠肺功能及肺组织病理学影响的研究. 中华医学杂志, 2015, 95(32): 2634-2638.
6.	贾晓鹏, 王海兵. 甘肃河西地区大气沙尘成分及影响分析. 中国沙漠, 2009, 29(1): 156-161.
7.	邵龙义, 李卫军, 杨书申, 等. 2002 年春季北京特大沙尘暴颗粒的矿物组成分析. 中国科学 D 辑: 地球科学, 2007, 37(2): 215-221.
8.	Lei FF, Luo WY, Dong ZB, et al. An investigation of the effects of dust storms on rat lung using HRCT and blood gas analysis. Sci Cold Arid Regions, 2016, 8(4): 319-324.
9.	Policard A, Collet A. Deposition of silicosis dust in the lungs of inhabitant of the Saharan regions. AMA Arch Ind Hyg Occup Med, 1952, 5(6): 527-534.
10.	李盛, 王金玉, 李普, 等. 沙尘天气的呼吸系统健康效应及机制研究进展. 环境与健康杂志, 2019, 36(1): 78-82.
11.	Craig VJ, Zhang L, Hagood JS, et al. Matrix metalloproteinases as therapeutic targets for idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol, 2015, 53(5): 585-600.
12.	Kang H. Role of microRNAs in TGF-β singling pathway-mediated pulmonary fibrosis. Int J Mol Sci, 2017, 18(12): E2527.
13.	Kasabova M, Joulin-Giet A, Lecaille F, et al. Regulation of TGF-β1-driven differentiation of human lung fibroblasts: emerging roles of cathepsin B and cystatin C. J Biol Chem, 2014, 289(23): 16239-16251.
14.	Ohno Y, Nakanishi T, Umigai N, et al. Oral administration of crocetin prevents inner retinal damage induced by N-methyl-D-aspartate in mice. Eur J Pharmacol, 2012, 690(1-3): 84-89.
15.	张伟, 郑建, 朱雪, 等. 益气类中药对肺纤维化大鼠模型肺组织中 TNF-α、IL-8 的影响. 中华中医药学刊, 2014, 32(10): 2311-2313.
16.	Yao HW, Xie QM, Chen JQ, et al. TGF-beta1 induces alveolar epithelial to mesenchymal transition in vitro. Life Sci, 2004, 76(1): 29-37.
17.	章巍, 刘新民, 李海潮, 等. 博来霉素致大鼠肺纤维化模型肺组织 MMP-2、MMP-9、MT1-MMP 及 TIMP-1、TIMP-2 的表达. 北京大学学报(医学版), 2002, 34(6): 716-721.
18.	Wang A, Wang F, Yin Y, et al. Dexamethasone reduces serum level of IL-17 in bleomycin-A5-induced rats model of pulmonary fibrosis. Artif Cells Nanomed Biotechnol, 2018, 46(4): 783-787.
19.	Yang D, Yuan W, Lv C, et al. Dihydroartemisinin suppresses inflammation and fibrosis in bleomycin-induced pulmonary fibrosis in rats. Int J Clin Exp Pathol, 2015, 8(2): 1270-1281.
20.	安方玉, 颜春鲁, 刘永琦, 等. 泻肺汤对肺纤维化大鼠 TGF-β1/Smads 信号转导通路的干预研究. 中华中医药杂志(原中国医药学报), 2018, 33(6): 2641-2645.
21.	胡洋, 李惠萍. PM2.5 对肺纤维化的影响. 临床内科杂志, 2015, 32(4): 228-230.
22.	Fujita H, Sakamoto N, Ishimatsu Y, et al. Effects of doxycycline on production of growth factors and matrix metalloproteinases in pulmonary fibrosis. Respiration, 2011, 81(5): 420-430.
23.	陈雅萍, 宋志芳. 尘源性炎症反应与矽肺纤维化的关系. 中国工业医学杂志, 1999, 12(2): 75-77.
24.	Zheng X, Qi C, Zhang S, et al. TGF-β1 induces Fstl1 via the Smad3-c-Jun pathway in lung fibroblasts. Am J Physiol Lung Cell Mol Physiol, 2017, 313(2): L240-L251.

1. 刘新春, 钟玉婷, 何清, 等. 塔克拉玛干沙漠腹地沙尘暴过程大气颗粒物浓度及影响因素分析. 中国沙漠, 2011, 31(6): 1548-1553.
2. Atkinson RW, Kang S, Anderson HR, et al. Epidemiological time series studies of PM2.5 and daily mortality and hospital admissions: a systematic review and meta-analysis. Thorax, 2014, 69(7): 660-665.
3. Cao XJ, Lei FF, Liu H, et al. Effects of dust storm fine particle-inhalation on the respiratory, cardiovascular, endocrine, hematological, and digestive systems of rats. Chin Med J (Engl), 2018, 131(20): 2482-2485.
4. 雷丰丰, 党雅梅, 张长青. 沙尘暴对大鼠肺组织影响的病理学观察. 中华病理学杂志, 2015, 44(3): 199-201.
5. 雷丰丰, 王学斌, 刘华. 沙尘气溶胶暴露对大鼠肺功能及肺组织病理学影响的研究. 中华医学杂志, 2015, 95(32): 2634-2638.
6. 贾晓鹏, 王海兵. 甘肃河西地区大气沙尘成分及影响分析. 中国沙漠, 2009, 29(1): 156-161.
7. 邵龙义, 李卫军, 杨书申, 等. 2002 年春季北京特大沙尘暴颗粒的矿物组成分析. 中国科学 D 辑: 地球科学, 2007, 37(2): 215-221.
8. Lei FF, Luo WY, Dong ZB, et al. An investigation of the effects of dust storms on rat lung using HRCT and blood gas analysis. Sci Cold Arid Regions, 2016, 8(4): 319-324.
9. Policard A, Collet A. Deposition of silicosis dust in the lungs of inhabitant of the Saharan regions. AMA Arch Ind Hyg Occup Med, 1952, 5(6): 527-534.
10. 李盛, 王金玉, 李普, 等. 沙尘天气的呼吸系统健康效应及机制研究进展. 环境与健康杂志, 2019, 36(1): 78-82.
11. Craig VJ, Zhang L, Hagood JS, et al. Matrix metalloproteinases as therapeutic targets for idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol, 2015, 53(5): 585-600.
12. Kang H. Role of microRNAs in TGF-β singling pathway-mediated pulmonary fibrosis. Int J Mol Sci, 2017, 18(12): E2527.
13. Kasabova M, Joulin-Giet A, Lecaille F, et al. Regulation of TGF-β1-driven differentiation of human lung fibroblasts: emerging roles of cathepsin B and cystatin C. J Biol Chem, 2014, 289(23): 16239-16251.
14. Ohno Y, Nakanishi T, Umigai N, et al. Oral administration of crocetin prevents inner retinal damage induced by N-methyl-D-aspartate in mice. Eur J Pharmacol, 2012, 690(1-3): 84-89.
15. 张伟, 郑建, 朱雪, 等. 益气类中药对肺纤维化大鼠模型肺组织中 TNF-α、IL-8 的影响. 中华中医药学刊, 2014, 32(10): 2311-2313.
16. Yao HW, Xie QM, Chen JQ, et al. TGF-beta1 induces alveolar epithelial to mesenchymal transition in vitro. Life Sci, 2004, 76(1): 29-37.
17. 章巍, 刘新民, 李海潮, 等. 博来霉素致大鼠肺纤维化模型肺组织 MMP-2、MMP-9、MT1-MMP 及 TIMP-1、TIMP-2 的表达. 北京大学学报(医学版), 2002, 34(6): 716-721.
18. Wang A, Wang F, Yin Y, et al. Dexamethasone reduces serum level of IL-17 in bleomycin-A5-induced rats model of pulmonary fibrosis. Artif Cells Nanomed Biotechnol, 2018, 46(4): 783-787.
19. Yang D, Yuan W, Lv C, et al. Dihydroartemisinin suppresses inflammation and fibrosis in bleomycin-induced pulmonary fibrosis in rats. Int J Clin Exp Pathol, 2015, 8(2): 1270-1281.
20. 安方玉, 颜春鲁, 刘永琦, 等. 泻肺汤对肺纤维化大鼠 TGF-β1/Smads 信号转导通路的干预研究. 中华中医药杂志(原中国医药学报), 2018, 33(6): 2641-2645.
21. 胡洋, 李惠萍. PM2.5 对肺纤维化的影响. 临床内科杂志, 2015, 32(4): 228-230.
22. Fujita H, Sakamoto N, Ishimatsu Y, et al. Effects of doxycycline on production of growth factors and matrix metalloproteinases in pulmonary fibrosis. Respiration, 2011, 81(5): 420-430.
23. 陈雅萍, 宋志芳. 尘源性炎症反应与矽肺纤维化的关系. 中国工业医学杂志, 1999, 12(2): 75-77.
24. Zheng X, Qi C, Zhang S, et al. TGF-β1 induces Fstl1 via the Smad3-c-Jun pathway in lung fibroblasts. Am J Physiol Lung Cell Mol Physiol, 2017, 313(2): L240-L251.

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The effect of dust fine particles on TNF-α, MMP, TGF-β₁, and collagens in the lung tissue of rats

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The effect of dust fine particles on TNF-α, MMP, TGF-β₁, and collagens in the lung tissue of rats