Preliminary study of exon sequence in pneumoconiosis using high-throughput and intervention of EGFR-TKIs on silicosis rats
10.3760/cma.j.issn.1001-9391.2019.06.002
- VernacularTitle: 表皮生长因子受体酪氨酸激酶抑制剂对大鼠尘肺纤维化干预的研究
- Author:
Hua ZHANG
1
,
2
;
Songquan ZHANG
1
,
2
;
Yan WANG
1
,
2
;
Chunling ZHANG
1
Author Information
1. Occupational Disease Department, Qingdao Central Hospital, Qingdao 266042, China
2. Respiratory Department, Qingdao Central Hospital, Qingdao 266042, China
- Publication Type:Journal Article
- Keywords:
Epidermal growth factor receptor;
Tyrosinase;
Silica;
Pathway;
Rats
- From:
Chinese Journal of Industrial Hygiene and Occupational Diseases
2019;37(6):408-415
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effect of epidermal growth factor receptor tyrosinase inhibitor (EGFR-TKIs) on silica (SiO2)-induced pulmonary fibrosis in rats, and to explore the role of epidermal growth factor receptor (EGFR) signaling pathway in pulmonary fibrosis.
Methods:A rat model of SiO2 silicosis was established (high, medium and low dose intervention groups, and the model group was infused with silica suspension). The control group was intratracheally injected with the same amount of sterile saline. The rats were intragastrically administered with different concentrations of EGFR-TKIs (13.5 mg/day, 6.75 mg/day, 3.375 mg/day). The model group and the control group were given the same amount of normal saline. Six rats in each group were euthanized on the 3rd, 7th, and 14th days after modeling. HE staining was used to observe the pathological of lung tissue. Masson staining to observe pulmonary fibrosis. Immunohistochemistry (IHC) expression of p-EGFR. Determination of hydroxyproline content by alkaline hydrolysis of the sample, Western Blot was used to detect the contents of TGF-α, Ras, p-Erkl/2, PI-3KCG and Aktl protein in lung tissue.
Results:The degree of fibrosis and hydroxyproline content in HE staining and Masson staining decreased with the increase of intervention dose, which was statistically significant (7 d, 14 d). Compared with the model group, the relative expressions of TGF-α, p-Erkl/2 and Aktl protein in lung tissue of each intervention group were statistically significant (P<0.05). The down-regulation of Ras and PI-3KCG protein in the high- and medium-dose intervention group was statistically significant (P<0.05), and there was no significant difference in the low-dose intervention group.Compared with the intervention group, the down-regulation of TGF-α, Ras, and p-Erkl/2 protein in the lung tissue was statistically different in the low-dose group (P<0.05). There was no significant difference between the dose and the medium dose intervention group (P>0.05). PI-3KCG was significantly different only in the high-dose intervention group and the low-dose intervention group on the 7th and 14th day (P<0.05), and there was no difference between the other groups (P>0.05). There was a statistically significant difference in Akt1 between the dose intervention groups (P<0.05).
Conclusion:EGFR-TKIs inhibits EGFR-related intracellular tyrosine kinase activity and intracellular phosphorylation, and inhibits the downstream signal transduction pathways of EGFR/PI-3K/AKt and Ras/ERK/MAPK target protein Ras, p-Erkl/2, PI3K, Akt1, thereby alleviating changes in pulmonary fibrosis, this process is dose-dependent, and the high-dose and medium-dose intervention groups have a significant effect.
