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Study On The Variation Of Inflammatory Factors In BALF Of Rats Exposed To Silicious Dust Early

Posted on:2012-07-15Degree:MasterType:Thesis
Country:ChinaCandidate:X B ZhouFull Text:PDF
GTID:2154330335479710Subject:Occupational and Environmental Health
Abstract/Summary:PDF Full Text Request
[Objective]To observe pathological changes in lung tissue of rats early, to analysis of the variation of inflammatory cells and factors, to explore the relationship with the pathological changes, to determine the early inflammatory biomarkers of silicosis.[Methods]We selected 168 male rats of Wistar and they were randomly divided into control group and dose of dust (15, 30, 60 mg/ml). The rats were set up the Silicosis model by non-indiscretion. We selected randomly 7 rats after exposed to silica dust on the 1th, 3th, 7th, 14th, 21th, 28th day in each group and the rats were sacrificed. The lung tissues were selected and stained by HE. Then we observed the pathological changes. Bronchoalveolar lavage fluid (BALF) was collected and we count the total number of inflammatory cells and classification ratio in BALF. We determined the cytokines (TNF-α, IL-1, IL-6, IL-16, MIP-1α, MCP-1, TGF-β) and nitric oxide and its derivatives ( nitrate/nitrite, nitrotyrosine) levels by enzyme-linked immunosorbent assay (ELISA).[Results]1. The variation of weight and Organ coefficient of the rats exposed to silica dust There was no significant difference in weight of rats in each group before exposed to silica dust (P>0.05). After exposed, the weight of rats in does group decreased compared with control group on the 7th day, and there was significant difference in weighe between in does group and in control group on the 28th day (P<0.05), but there was no significant difference among in the high, medium and low dose group. There was no significant difference in does group and in control group.2. Observations the pathological changes of lung tissueIn the control group, the lung tissue appeared hyperemia, edema and inflammatory cells increased on the 1-3th day. On 7th day, inflammation gradually disappear, and on the 14th day lung tissue returned to normal. In dose of dust, the lung tissue appear congestion and inflammatory cell infiltration on the 1-3th day; widened alveolar septum edema, inflammatory cell accumulation, mainly macrophages and neutrophils on 7th day; part of the structural damage to lung tissue on the 14th day; destroyed most of the alveolar structure and inflammatory cells mainly lymphocytes on the 21th day; severe alveolar structural damage, occasional fibroblasts on the 28th day.3. The change inflammatory cells in ratsThe total number of leukocytes in BALF in the dust group, was significantly higher than the control group on the 1th, 3th, 21th, 28th day, there was significant difference between in high dose group and in control group (P<0.05); the total number in does group decreased in control group.At each time point, the number of macrophages in each dose group in BALF decreased compared with the control group, but it was no statistical significance. The number of neutrophils in each does group significantly higher than those in control group in 17 days (P<0.05 ), and in 1428 days it decreased slightly than in the control group, but the difference was not statistically significant. There was no difference in the number of lymphocytes between in the control group and in does group in 17 days, in 1428d the number in each does group was significantly higher than in the control group (P<0.05). In the dose Group at each time point the number of dust cells was significantly higher than those in the control group (P<0.05), and the dust cells tended to increase with the increasing doses of dust. 4. Changes of inflammatory factor in BALFThe concentration of Cytokines (TNF-α, IL-1, IL-6, IL-16, MIP-1α, MCP-1, TGF-β) and nitric oxide and its derivatives in each dose group at time points increased than in the control group, the difference statistically was significant (P<0.05), on the 14th day it reached the peak value. The difference changes of IL-1 and TNF-αwas significant early, the dose-response relationship was significant. The different changes of IL-6, IL-16 and TGF-βwas significant late; the change of MCP-1 and inflammatory cells was the same trend; MIP-1αand other Cytokines was correlation significantly (P <0.01). The dose-response relationship of NO2-/NO3- was obvious, but nitrotyrosine was not obvious. NO2-/NO3- and Nitrotyrosine were significantly related.[Conclusions]1. Early in the formation of silicosis (128 day), the histopathology change of lung appeared mainly: the inflammatory cell aggregated and infiltrated in the lung, alveolar septum was thicker, fibrous tissue began to proliferate, the normal lung tissue changed.2. The rats exposed to silicious dust early appeared major the acute inflammation, and macrophages, alveolar neutrophil infiltrated and aggregated in alveolar space, the proportion was significantly higher; in the later stage it was the chronic inflammation, lymphocyte infiltrated and aggregated, the proportion increased; dust cells was to increase with the increase of dose dust, and it has a good dose - response relationship.3. The changes of IL-1 and TNF-αearly was significant, they mainly involved in the early inflammatory response; the changes of IL-6, IL-16 and TGF-βwas significant late, and they promoted the development of pulmonary fibrosis; the chemokines of MCP-1 and MIP-1αwith the inflammatory cells and other cytokines had a good correlation, they interaction with each other and form a complex network, in the development of silicosis it played an important role. It is feasible that these cytokines have already been taken as a marker for early detection of silicosis. The content of NO2-/NO3- and the inflammatory process silicosis had good synchronization and a better dose-response relationship. NO2-/NO3- can be used as inflammatory markers of early silicosis; the content of nitrotyrosine was later than NO2-/NO3-, Dose-response relationship was not obvious, and it can be used as a reference biomarkers of silicosis inflammatory response early.
Keywords/Search Tags:Silicosis, pathology, early inflammation, cell factor, nitric oxide
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