The Mechanisms And Early Biomarkers Of Pulmonary Fibrosis By Silica Particles

Silicosis, a type of systematical disease caused by inhalation of silica dust characterized mainly by pulmonary interstitial fibrosis, has been stipulated by laws as an occupational disease. During 1991 to 2002, a survey focusing on the incidence of occupational diseases in our country revealed that the incidence of occupational diseases showed a remarkable concave-shape rebounding tendency. The number of episode was about 22 thousand per year in the early 90s of the previous century, and then dropped to 10 thousand at the end of 1997, but then rose to 15 thousand in 2002. This tendency is ascribed to the markedly rising rate of the detection rate of pneumoconiosis that is still in severe condition. Up to 2002, the nationwide accumulative number of pneumoconiosis checked out has reached 580 thousand cases, in which there are about 140 thousand deaths of pneumoconiosis, and about 440 thousand people suffering from pneumoconiosis. The high incidence of pneumoconiosis is characterized mainly by the pneumoconiosis and silicosis of colliers. However, if they stop exposing to silica dust, the disease is still developing as usual; meantime, exposure to high concentration of silica dust can result in shortened attack time of length of service, attack in younger age, severe state of the illness, and high incidence of death. It is estimated that the disease causes a great loss up to 9 billion per year to the country. The statistical data obtained in 2001 showed 6 million workers exposed to dust. According to the law of the occupational disease prevention and treatment, the number of workers compulsively undertaking occupational physical examination per year amounts to 4 million. Moreover, with the development of economy, a large number of labors from the countryside are engaged in this type of dust-exposed work without any healthy protection. As a result, the number of dust-exposed workers is rising tremendously. The plan put forward by the ILO and WHO to eliminate the global silicosis aims to decrease significantly the incidence of silicosis in 2010, and to eliminate completely the disease by the year of 2030. In China, the number of patients suffering from pneumoconiosis and the number of dust-exposed workers rank the first in the world. In addition, the poorly known pathogenic mechanisms of pneumoconiosis result in no specific indexes for early diagnosis, nor specific therapeutic methods or medication. By a photograph taken with x-rays of back-chest postion diagnosed,the silicosis have no method to recovery.As a result of that, it can be said that there is still a long way to go for the control of the disease. Therefore, further investigation of the mechanisms of silica dust in pulmonary fibrosis and the selective biomarkers applied for the early diagnosis is very significant for the prevention and treatment, and even for the complete elimination of the disease. Objective This study was designed to investigate the expressions of cytokines such as transforming growth factor-β1, tumor necrosis factor-α, inductive nitricoxide synthase, and nucleus factor-κB , and their regulatory effect on the abnormal synthesis of extracellular matrix (ECM) Ⅰ and Ⅲ collagens in pulmonary fibrosis; to study the apoptosis induced by silica dust and the mechanisms at the whole level and protein fingerprints and the selective biomarkers for the early diagnosis of pulmonary fibrosis; and to explicit the mechanism of silica dust induced pulmonary fibrosis for the purpose of providing the new methods for the early diagnosis and treatment of pulmonary fibrosis. Methods Wistar rats were randomized into two groups: control group and experimental group. After the rat model of silicosis was established by intratracheal infusion of silica dust suspension, eight rats from each group were sacrificed at 1, 3, 7, 14, 21, and 28 d. (1) The expressions of TGF-β, TNF-α, iNOS, NF-KB, and Fas-L receptor in the tissue of the model rats were detected by tissuechip microarray and immunohistochemistry. The abnormal synthesis of collagens Ⅰ and ?...