1060 Role of endoplasmic reticulum stress in the intervention effect of polyg to silicotic fibrosis in rats

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Abstract

Background

Silicosis is a kind of serious occupational disease caused by inhalation of silicon dioxide dust in the professional activities for a long term, and its basic pathological features mainly include pulmonary inflammation and diffuse fibrosis. Scholars have poured much energy into research and put forward a variety of hypotheses about the mechanism of silicotic fibrosis, and the apoptosis of lung cells is considered as one of the most important mechanism of silicosis fibrosis. Endoplasmic reticulum stress is one of the important signal pathways mediating cell apoptosis, and it has been proved to be associated with many diseases. But there is still little knowledge about the relationship between endoplasmic reticulum stress and silicotic fibrosis. Our previous study found that PolyG has preventive and therapeutic effect on pulmonary fibrosis in rats, however the mechanism about the intervention effect of PolyG on silicotic fibrosis is still unclear.

Objective

To investigate the role and the mechanism of endoplasmic reticulum stress in the intervention effect of polyuridylic acid (PolyG) on silicotic fibrosis in rats.

Methods

Eighty SD rats were randomly divided into saline group, silicosis model group, PolyG prevention group and PolyG treatment group, building the animal model of silicosis with non exposed tracheal method except saline group. Rats in prevention group were given PolyG on the day after dusts and were sacrificed at 28 d and 56 d time point after given PolyG, 8 rats were sacrificed in each group.Rats in treatment group were given PolyG at 28 d after dusts and were sacrificed at 28 d and 56 d time point after given PolyG, 8 rats were sacrificed in each group. At 28 d, 56 d and 84 d time point after dusts, rats in saline group and silicosis model group were sacrificed (8 rats were sacrificed in each group) as the negative and positive groups at the same time. The pathological changes of lung tissue was observe by hematoxylin eosin staining and Masson staining, detect the expression level of endoplasmic reticulum stress and apoptosis related proteins IRE1, GRP78, CHOP, PERK, ATF6, casepase3 and casepase12 in lung tissue by Western blot.

Results

In saline groups, the structure of lung tissue was normal, some showed mild inflammation and there is no silicotic nodule and collagen deposition, the lung tissue in silicosis model groups showed the alveolar structure were severely destructived, and it occurred a lot of silicotic nodules and collagen deposition, most lung tissue in this groups have typical fibrous nodules, and along with the extension of exposure, the nodules gradually fused and formed clumps. But the silicotic nodules and collagen deposition in PolyG prevention group and PolyG treatment group were markedly reduced, most of the nodules disappeared, just showed the inflammation in the lung tissue. At 28 d and 56 d time point after prophylactic use polyG, the expression level of IRE1, GRP78, CHOP, PERK, ATF6, casepase3 and casepase12 in prevention group were lower than the same period of silicosis model group (p<0.05), compared with 28 d PolyG prevention group, the expression level of each protein was decreased in 56 d PolyG prevention group, but it has no statistical significance (P>0.05). 3. At 28 d and 56 d time point after Therapeutic use polyG, the expression level of IRE1, GRP78, CHOP, casepase3 and casepase12 in treatment group were lower than the same period of silicosis model group (p<0.05), compared with 28 d PolyG treatment group, the expression level of each protein was decreased in 56 d PolyG treatment group, but it has no statistical significance (P>0.05). 4. The expression level of each protein in PolyG prevention group were lower than the PolyG treatment group, the expression level of GRP78, PERK, ATF6, casepase12 and casepase3 was significantly different between PolyG prevention group and PolyG treatment group (p<0.05), the different expression level of IRE1 and CHOP in this comparison closed significant level(p=0.056, p=0.055).

Conclusion

The endoplasmic reticulum stress participate in the mechanism of the intervention effect of PolyG to silicosis fibrosis in rats, PolyG can be effective in the prevention and treatment of silicosis fibrosis, and we will get more significant effect by preventative using PolyG, both the short-term and long-term intervention effect of PolyG on silicotic fibrosis are well.

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