The Role Of Prxs In Pulmonary Fibrosis Induced By Silicon And Quercetin Prevention Effect

Objectives Silicosis（silicosis）is a systemic diseases and character with pumlaryfibrosis induced by silica exposure. Studies have shown that antioxidant balancedisorders is currently one of the mechanism of silica induced lung tissue fibrosis.Peroxiredoxins（Prxs） is a newly discovered type of peroxidase, belongs to theantioxidant protein superfamily. Prxs is proved to be with ability of removing freeradicals, and then protect sensitive protein. A lines of studies showed that Prxs proteinplay an important role in tumorigenesis, However it has not been reported about its rolein silicosis. Quercetin（quercetin, QU; three, four, five,’3’,4’25hydroxy flavonoids）and its derivatives are flavonoids with biological activity including removalling freeradicals, anti-fibrosis and protecting blood vessels. But its preventive effect onpulmonary fibrosis induced by silica has not been reported.Therefore, The currently studyfouced on PrxsⅠ and Prxs Ⅵ roles during the development of pumlary fibrosis.silicosis model was used to explore Prxs protein expression on the pathogenesis ofsilicosis. our data will not only enrich the mechanism of silica induced lung tissuefibrosis, but also provide the basis for clinical treatment based on exploreing theintervention effect of quercetin.Methods1Experimental animals and grouping: Sixty healthy adult male SPF rats wereraised in the barrier animal laboratory.（1）The role of Prxs protein on the pathogenesisof silicosisThirty two rats were randomly divided into four groups, namely the controlgroup, low dose group, middle dose group, high dose group（each group for8rats）.Rats in the control group were given1ml saline via trachea. Rats in silca groups weregive silica solution for1ml at dose of12.5mg/ml and25mg/ml and50mg/ml respectively.（2）Quercetin Intervention studyTwenty four rats were randomly divided into controlgroup, silica and Quercetin group. Rats in silica groups and Quercetin group were givensilica solution for1ml at dose of50mg/ml. meanwhile rats in Quercetin group were givenquercetin of50mg/kg every day through oral.2Antioxidant enzymes detection: Theactivities of catalase（CAT） and glutathione peroxidase（GSH-Px）and H2O2contentwere detected by using the kits.3PrxsⅠ and Ⅵ protein expression: Using Western blotmethod to detect antioxidants Prxs Ⅰ and Ⅵ expression level in lung tissue.4HEstaining was used to observe lung tissue pathology, Masson staining was applied toobserve collagen deposition of lung tissue. At the same time level of hydroxyproline（HYP）were detected by kits.5Statistical analysis: Statistical analysis: All data wereshowed x sand SPSS17.0statistical analysis software was applied. The proteinexpression level was showed with relatively data, which are divided by the number of thecontrol group. Comparing multiple samples of each group was used single factor analysisof variance（One Way ANOVA）.Results1Pathology data showed that cells nodules was seen in lung tissue after twentyeight days silica exposure, indicating that Silicosis rat model was established successfully.Masson staining method was applied to the lung tissue collagen fibers of observation, theresults show that with the increase of silica exposure, collagen fiber increased.2 Different silica doses on the expression of HYP content in lung tissue of rats: With theincrease of silica dose, the expression of HYP content in lung tissue increased（P <0.05）, and the expression of HYP content was positively correlated with the silicadose（r=0.882，P=0.028）, suggesting that the degree of pulmonary fibrosis in ratsincreased with silica dose.3The influence of different silica exposure on the activities ofcatalase（CAT）and glutathione peroxidase（GSH-Px）and H2O2content.（1）Thelevel of H2O2: Compared with control, the H2O2level in high dose group and middle dosegroup increased36.30%and36.30%, and the differences were significant（P <0.05）,indicating that the H2O2content in the lung tissue of rats increasing with silica dose.（2）The activities of catalase（CAT）and glutathione peroxidase（GSH-Px）:Compared with control, the CAT level in high dose group and middle dose group reduced35.36%and21.39%, the GSH-Px level in high dose group and middle dose groupreduced39.69%and16.24%, the differences were significant（P <0.05）, suggestingthat the degree of oxidative damage in rats increased with silica dose.4Different silicadoses on the expression of PrxsⅠand PrxsⅥ content in lung tissue of rats: Comparedwith control group, the PrxsⅠlevel in three silica group reduced12.00%,15.00%and12.00%; Compared with control and low dose group, the Prxs Ⅵ level in high dosegroup reduced18.00%and14.58%, the difference were significance（P <0.05）.5Quercetin intervention on the expression of HYP content in lung tissue of rats: Comparedwith control, the HYPlevel in silica group increased39.02%. Compared with silica group,the HYP level in quercetin group reduced24.56%（P <0.05）, indicating that inpulmonary fibrosis caused by silica dust joining quercetin could reduce the level of HYPcontent in lung tissue.6The influence of quercetin intervention on the activities ofcatalase（CAT） and glutathione peroxidase（GSH-Px） and H2O2content. Comparedwith silica group, the H2O2level in quercetin group reduced15.24%(P <0.05）,indicating that in pulmonary fibrosis caused by silica dust joining quercetin could reducethe level of H2O2content in the lung tissue. Compared with silica group, the CAT andGSH-Px level in quercetin group increased by31.31%and20.45%（P <0.05）, Showedthat the addition of quercetin can reduce the activity of CAT and GSH-Px, the lung tissuewhich caused by the silica dust in pulmonary fibrosis.7Quercetin intervention on theexpression of PrxsⅠand Prxs Ⅵ content in lung tissue of rats: Compared with silicagroup, the PrxsⅠand Prxs Ⅵ level in quercetin group increased28.77%and21.00%,differences were significant（P <0.05）.Conclusions1Prxs protein migh involved in the process of pulmonary fibrosis causedby silica exposure.2Quercetin treatment can decrease the development of pulmonaryfibrosis induced by silica exposure.