Research On Variation Of CTGF And KL-6 In The Development Of Silicosis

?Objective?To investigate the changes of CTGF and KL-6 in the process of silicosis and its effect,and to give some theoretical support for the diagnosis and treatment of silicosis and its effect evaluation.?Methods?1.Animal experiments: SPF clean grade Wistar male rats were randomly divided into two groups of experimental group and control group(7,14,21,28,60,90 d after exposure)and control group.Lung tissues were dissected and serum and BALF were collected.The expression levels of CTGF and KL-6 in the lung tissue samples were determined by Hematoxylin and eosin and immunohistochemistry.The mass concentrations of CTGF and KL-6 in serum and BALF were measured by ELISA.The concentration of silicon in serum was measured by atomic absorption spectrometry.2.Population studies:A total of 180 workers from one of the Shandong Province gold mine were chosen as object of observation.Among which 40 patients at silicosis stage ? and40 patients at silicosis stage ? were divided into silicosis stage ? group,silicosis stage ?group,21 patients at silicosis stage ? and another 39 workers exposed to silica dust without suffering from silicosis Clinical symptoms,were chosen as group of dust exposed,and 40 logistical workers without being exposed and history of silicosis' s illness were chosen as control group.And apply the ELISA to access the level of connective tissue growth factor(CTGF)and type ? alveolar cell surface antigen(KL-6),in the serum from subjects.Calculate the cumulative dust exposure(CTE)of each group of workers to investigate the correlation between CTE and CTGF and KL-6 levels in each period.3.Analysis of Dosage in Dust:The contents of the serum silicon and lung tissue homogenate were measured by atomic absorption spectrometry,and the correlation analysis was made.The concentration of serum silicon of patients with silicosis was measured.The correlation between silicon,CTGF and KL-6.?Results?1.Experimental study on the effect of CTGF and KL-6 on the development of silicosis1.1 Changes of serum CTGF and KL-6 contents in BALFThe levels of CTGF in BALF and serum were higher than those in the control group at different time points,and the difference was statistically significant(P<0.05)The level change of CTGF,KL-6from BALF and serum.1.2 Pathological changes of lung tissue in rats exposedThe lungs were soft and the color was ruddy and elastic in the control group.HE staining was used to observe the normal lung tissue and alveolar structure,then was mild inflammation;at the 7th day,28 d when the majority of the alveolar cavity disappeared,bronchial wall thickening,inflammatory cells mainly lymphocytes and plasma cells,occasionally fibroblasts;90d alveolar cavity structure blurred,morphological changes,fibroblasts appear in large numbers Significant fibrosis.1.3 Immunohistochemical staining of lung tissueThe expression of CTGF in the lung tissue of the silicosis rats was higher than that in the control group(P<0.05).The expression of CTGF protein in the lung tissue of the silicosis rats was higher than that in the control group(F=4.006,P<0.05).The difference was statistically significant(P<0.05)at 14 th,21th and 28 th day.KL-6 was mainly secreted by type ? alveolar epithelial cells(proliferation,regeneration or damage).The results showed that the expression of KL-6 protein group was higher than that of control group(F=3.175,P<0.05)28th,60 th and90th day were statistically significant(P<0.05).With the extension of time,the expression of protein showed a gradual increase trend.2.The epidemiological study of pulmonary fibrosis related factors CTGF and KL-6 in the development of silicosis.2.1 Changes of CTGF and KL-6 in serum of patients with Silicosis in different periodsCompared with the control group,the concentration of CTGF in the sera of patients with stage ? silicosis reached the peak,but it was higher than that of the control group.Compared with the control group,the difference was obvious between the two groups and the silicosis patients(P<0.05).There was no significant difference between the two groups(P>0.05).There was no significant difference between the two groups(P>0.05).Compared with the control group,the serum levels of KL(P<0.05).The difference was statistically significant(P<0.05),and the difference was statistically significant(P<0.05),and the difference was statistically significant(P<0.05)Group,the difference was statistically significant(P<0.05).2.2 Correlation between cumulative total dust exposure(CTE)and pulmonary fibrosis related factors CTGF and KL-6The CTGF and KL-6 contents in the control group,the dust group,the silicosis stage ?,the silicosis stage ? group and the silicosis group ? were stratified according to the cumulative total dust exposure(CTE)and found that there was no correlation with these two factors(P>0.05).3.Analysis of dust exposure dose(Content of serum silicon)The content of silicon in serum was also decreased in the case group(P<0.05).The content of silicon in the serum of the rats exposed to silica was decreased with the prolongation of the dying time(P<0.05).The correlation between the content of silicon and CTGF and KL-6 in serum of silica-infected rats showed that there was a positive correlation with the concentration of CTGF(r=-0.313,P<0.05),and there was a positive correlation between the serum and the content of silicon in the lung tissue homogenate(r=0.696,P<0.05),and there was a negative correlation with the KL-6(P <0.05).In the epidemiological survey,the population of each group was stratified by the concentration of blood and then correlated with the concentration of CTGF and KL-6 in serum.The results showed that serum(rCTGF=-0.428,PCTGF<0.05;rKL-6=-0.550,PKL-6<0.05).There was no correlation between the dust group and the other group(P>0.05).?Conclusions?1.HE changes of CTGF and KL-6 in BALF,serum and lung tissues were consistent with that of lung tissue and the results of immunohistochemical staining,indicating that CTGF and KL-6 play a role in the development of silicosis.2.The levels of CTGF and KL-6 in the serum of patients with silicosis were significantly different from those in the treatment of silicosis,and the CTGF and KL-6 contents did not exist Relevant,indicating that the cumulative dust exposure may be due to the presence of external exposure instability,individual differences lead to actual inhomogeneities,etc.3.The change in the content of silicon in the serum of rats exposed to dust and different times suggests that it is the possibility of exposure to silica,and the correlation between serumsilicon concentration and serum CTGF and KL-6 levels suggests that there may be dose between them Response to further provide a theoretical basis for biomarkers of silicosis early diagnosis.