| dc.description.abstract | Tobacco smoking is a recognized risk to human health, and more than 7000 chemical compounds have been identified. Moreover, cigarette smoking has been considered to be a risk factor for developing chronic obstructive pulmonary disease (COPD), which is an important health problem in the world. Mainstream cigarette smoke (MS) is a major concern for smokers, and the sidestream cigarette smoke (SS) could influence the neighboring people through passive smoking. In addition to the chemical composition, particle size, number concentration, surface area, morphology and charging status might also be important parameters affecting the health effects and the deposition fraction in the respiratory system. To estimate the inhalation dose of cigarette smoke particles in different regions of the lung, international commission on radiological protection model (ICRP) and multiple path particle dosimetry model (MPPD) are generally used and the aerosol physical properties were required as input parameters, which, however, were not comprehensively investigated in the past. In this study, the aerosol physical properties of cigarette smoke particles (including particle size distribution, mass concentration, concentration of black carbon, particle surface area concentration deposited in the alveolar region and effective particle density) are thoroughly characterized and studied for the dose of respiratory deposition, and applied to mice exposure model. To avoid the effects of cigarette smoke particles coagulation or aging, the measurements were mostly performed in situ and reported in real-time. The effective density of MS and SS cigarette particles was measured by both traditional DMA-APM system and APM-SMPS system (with improved temporal resolution). The effective particle density was found to be independent of particle mobility size, which suggested that the particles could be spherical. The novel tandem DMA-AE33 system was established to provide the size-selective BC and UVPM mass concentrations of cigarette smoke. These parameters were used for calculating the deposition fraction of cigarette smoke in MPPD. The results show the deposition fraction of mice for MS particles were 0.52, 0.02, 0.01 and 0.55 for head, trachea and bronchi (TB), alveoli and total region, and those for SS particles were 0.47, 0.03, 0.04 and 0.54. Some of these aerosol characteristics of cigarette smoke particles are first time being revealed and valuable for lung deposition and inhalation toxicity studies.
The smoker’s inflammatory cells would increase lung epithelial cells’ ageing, death, poor cilia function and the formation of emphysema, and regulation of autophagy is associated with them. Clinically, glucocorticoid is commonly used for severe COPD with acute exacerbation; however, glucocorticosteroids insensitivity is often occurred in severe COPD. Our study to investigate the association between used corticosteroids treatment and lung inflammation in mice. After exposure, we collected lung tissue of mice to study the biological responses (Total Protein、LDH、8-Isoprostane、IL-8、Western Blot). LC3BⅡ/Ⅰ ratio was significantly reduced by use of glucocorticoid in COPD mice. The results suggest that COPD mice were insensitive to glucocorticosteroid. When autophagy was inhibited by 3-Methyladenine (3MA), there were no significant increased in LDH, 8-isoprostane and IL-8 by glucocorticosteroid. Previous researches indicated that when autophagy was inhibited by 3-MA, there was reduced in IL-8. Therefore, our study levels of IL-8 and LC3BⅡ/Ⅰ ratio were significantly increased by glucocorticosteroid at COPD mice. When autophagy was activated by Torin 1, there was increased in LC3BⅡ/Ⅰ ratio by glucocorticosteroid, To indicate the Autophagy helped to remove accumulated harmful substances, reduce the production of ROS and inhibit inflammation, but there were no reduced in 8-isoprostane and IL-8.The results show an association between autophagy and glucocorticosteroid in inflammation, which could be applied to glucocorticosteroid insensitivity in COPD mice. In conclusion, autophagy may regulate glucocorticoid sensitivity in COPD.
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