The Changes Of Apoptosis And Proliferation And The Preliminary Study Of Its Mechanism In The Model Of Rat Silicosis

Objective To explore the changes of apoptosis and proliferation of cells in lung tissue of rat with silica instillation, and their significance in silicosis, to clarify the role of activated MAPK and caspase-3 in the apoptosis and proliferation progress.Methods 48 rats were randomly divided into saline control groups and silica instillation groups, and silicosis model was established in rats. Flow cytometry was used for detecting the rate of apoptosis at various stages; Immunohistochemistry for the expressions of PCNA, phosphorylated MAPK and cleaved capspase-3.Results The model of rat silicosis was made successfully. The apoptosis rate in experimental group was significantly higher than that in control group, and was increased with time-dependence. PCNA was mainly expressed in alveolar epithelium cells, pulmonary macrophages and inflammatory cells. The positive expression of PCNA began to appear on the 3rd day, and reached a peak level on the 14th day and kept high level for 14 days. On the 28th day, PCNA was expressed mostly in fibroblasts. There was significantly positive relation of cell apoptosis to cell proliferation(r=0.86,P<0.01). P-MAPK was expressed in alveolar epithelium cells, pulmonary macrophages and endothelial cells, and its expression intensity reached top level on the 7th day. The expression ofp-MAPK in experimental group was stronger than in control group. The expression strength of p-MAPK was closely positive correlated with cell apoptosis and proliferation(r=0.447, P<0.05; r=0.68, P<0.01). Cleaved caspase-3 was mainly expressed in alveolar epithelium cells, pulmonary macrophages and infiltrated inflammation cells. The expression strength of cleaved caspase-3 in experimental group was stronger than in control group, but its expression intensity was not related to the cell apoptosis (r=0.215,/?0.05). Conclusions1. The cell apoptosis was increased in parallel with its proliferation in lung tissue during rat silicosis genesis.2. p-MAPK not only regulates proliferation but also do apoptosis in the pulmonary fibrosis progress.3. Besides caspase-3, there may be other protein factors to play important roles in regulating cell apoptosis during rat silicosis genesis.