| The continued energy consumption and population expansion are always accompanied with worsening air pollution. In recent years, regional haze affects human health seriously, which was spreading to wider and becoming more severe than before. In January 2013, the haze swept more than 10 provinces in the east, northeast and southwest areas of China. Beijing was the most contaminated areas. The average haze contaminated days reached 21.7 in 31 days of January. The highest hourly concentration of PM2.5 reached 680 μg/m3. High concentrations of suspended particulate matter in the atmosphere is one of the important reasons of haze, especially fine particles (PM2.s).With the development of industry and transportation, the concentration of PM2.5 will keep a uptrend in recent years. Many epidemiological and toxicological data shows a positive association between particulate matters and adverse health effects. This adverse health effects involved in respiratory system, cardiovascular system, nervous system, immune system and so on. However, the mechanism underlying the PM-induced adverse health affects is not clear. Therefore, study on the respiratory effects of PM2.5 is of great significance.Particulate matter is a mixture of complicated composition. The chemical composition of PM varies greatly as the combustion sources, climate, season and type of urban or industrial pollution. The major components of PM are carbonaceous component, organic compounds, transition metals, ions, and materials of biologic origin. In this study, PM2.5 is collected from traffic area of Shanghai in winter. We had detected 17 kinds of inorganic elements in this particle. The concentrations of these elements is 1961.62 ng/m3, of which the most abundant elements are Ca, Fe, K, Na and Al. The metals which are harmful to human health, such as Pb, As, Cu and Cr, accounted for 3.0% of inorganic elements of PM2.5.The concentration of water-soluble ions is 22.21 μg/m3, of which SO42-, NH4+, NO3- and Cl- accounted for 92.9% of the totals. The concentrations of organic carbon (OC) and elemental carbon (EC) are 0.021 μg/m3 and 0.008 μg/m3 respectively. The level of organic elements reached 517.9 ng/m3, the concentration of polycyclic aromatic hydrocarbons (PAH) is about 30.0 ng/m3.C57BL/6 male mice is treated as experiment subjects, which receive acute and sub-chronic PM2.5 exposure by intratracheal instillation. The purpose of the study is to explore toxic effects of fine particulate matters (PM2.5) from two aspects including inflammation and oxidative stress on lung, as well as changes of Thl7/Treg balance.The first part of our study is acute exposure test. Thirty-two C57BL/6 male mice are randomly divided into four groups including one saline control group and three PM2.5 exposure groups (1.5、7.5、15 mg/kg BW, respectively). Each group received intratracheal instillation three times for 3 consecutive days. Bronchoalveolar lavage fluid (BALF) was collected for biochemical analysis. The cytotoxicity markers (LDH and AKP) and permeability markers (TP and ALB) were measured to examine lung injury. The percentage of macrophages, neutrophils and lymphocytes, the Th17-and Treg-related cytokines in BALF were measured as inflammation indicators. The activities of SOD and MDA in BALF were measured as oxidative stress indicators. The results showed that the levels of LDH, AKP, TP and ALB in exposure groups were significantly higher than those in saline control group, and dose-dependent relation was observed in all these indexes. The amout of IL-6, IL-17, IL-10 and TGF-P increased dose-dependently in BALF. The results of IL-10 is different in sub-chronic exposure groups, IL-10 increased dose-dependently in acute exposure test, indicating that the organism was still at a Self-repairing stage, and proliferation and differentiation of Treg cell were stimulated, and then Treg secreted IL-10 which played a Inhibition role of the development of inflammation response at the initial stages of the PM2.5 exposure. Compared with control group, The level of MDA significantly increased in PM2.5 exposure groups, the level of SOD was just the opposite. H-E stained lung sections presented characteristic histological aspects related to PM2.5 exposure, including neutrophil and lymphocyte infiltration around terminal tract and alveolar walls and falling off of epithelial cells. Oxidative stress and inflammation which induced by PM2.5 acute exposure could damage the alveolar-epithelial barrier and lung parenchyma toxicity.The second part of our study was sub-chronic exposure test. Animal groups and exposure dose are the same as acute exposure test. Each group received intratracheal instillation twice per week for 3 consecutive months. The histopathological examinations showed that PM2.5 could cause inflammary injury and this injury was more noticeable with the increase of dosage and prolong of exposure time. The total number of cells, the percentage of neutrophils increased obviously in exposure groups, the percentage of macrophages was just the opposite. The level of IL-6, IL-17, TGF-P in BALF was up-regulated in exposure groups, but the levels of IL-10 was down-regulated compared with the control group. That indicated pulmonary immune balance was broken by the chronic PM2.5 exposure. So that the proliferation, differentiation and secretion function of Treg cells could not sustain, then the level of IL-10 reduced. All these changes impaired immune suppression function, and resulted in persistent, chronic inflammatory injury in lung. The level of Th17-specific transcription ROR-γt increased and The level of Treg-specific transcription Foxp3+ decreased. The result consistent with the level of cytokines in BALF, indicating lung inflammation caused by PM2.5 broke the balance of Th17/Treg. Th17 plays an important role in PM2.5 induced lung inflammation and immune injury. |
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