Effect Of Exposure To PM2.5 Via Endoplasmic Reticulm Strss To Induced Apoptosis Of Lung Cells On Rats With COPD

Objective:To investigate whether exposure of PM2.5 activates the endoplasmic reticulum stress pathway to induce the apoptosis of lung structure and its effect on rats with COPD.Methods:The 40 healthy male SD rats(body weight 200 ± 20g) were randomly divided into control group(group N), PM2.5 group(group P),COPD model group(group C),COPD+PM2.5 group(group C+P).The COPD rats model was built by the two times of smoke and the injection of lipopolysaccharide(200ug/100ul). On the basis of constructing COPD model, the C+P group was injected with PM2.5 suspension(5mg/kg, volume0.25ml/kg), the rats in group P were injected with the same amount of PM2.5 suspension and the same volume of normal saline was injected into the trachea of the rats in group N.After the model was established, the lung function of rats in each group was detected.HE staining was performed to observe the pathological changes of lung tissue in each group. TUNEL method was used to measure the degree of apoptosis of lung cells.The expression of GRP78, ATF6 and CHOP protein in lung tissue was detected by immunohistochemistry, and the expression level of m RNA CHOP was detected by real-time RT-PCR.Results:1.Lung function: Group C and group C+P FEV0.3/FVC(%), peak expiratory flow(PEF)were compared with group N and P group decreased obviously, which C+P group compared with the C group is further reduced(P < 0.05), while group P and group N comparison results still can not believe that differences were statistically significant(P >0.05).2.HE staining: the normal structure of lung tissue in N group.P group of lung tissue structure integrity, alveolar septum damage is not obvious, compared with the N group, the bronchial wall around the obvious inflammatory cell infiltration.The lung tissue structure of C group was not complete, the damage was obvious, the alveolar wall became thin, and the alveolar space was enlarged,Some of them formed into Bullaes,Bronchial epithelial cell necrosis and partial loss,there are a large number of inflammatory cell infiltration around the wall of the tube.The lung tissue structural damage in C+P group was more serious than that in C group.3.lung tissue cell apoptosis:The apoptosis rate of P group, C group and C+P group was higher than that of N group(P < 0.05).The apoptosis rate of C group was significantly higher than that of group P(P<0.05).Compared with group C+P,the C group was further increased(P<0.05).4.immunohistochemistry:GRP78, ATF6 and CHOP were mainly expressed in bronchial epithelial cells, alveolar epithelial cells and vascular endothelial cells.The former two are mainly expressed in the cytoplasm, the latter is mainly expressed in the cell nucleus.The expression of GRP78, ATF6 and CHOP protein in lung tissue of N group was little.The expression of these three proteins in P group, C group and C+P group were higher than those in group N(P<0.05).The C group was significantly higher than that in the P group(P<0.05).Compared with the C group, the C+P group was further increased(P<0.05).5.real-time RT-PCR results:The expression levels of m RNA CHOP in group P, group C and group C+P were higher than those in group N(P<0.05).The C group was significantly higher(P<0.05) than that of the P group.C+P group compared with the C group was further increased(P<0.05).Conclusion:PM2.5 exposure can activate the endoplasmic reticulum stress pathway to induce the apoptosis of lung structure,and further promote the development and aggravation of the disease of COPD rats.