The Effect Of Exogenous Hydrenous Sulfide On Bleomycin-induced Pulmonary Fibrosis And The Expression Of IL-6,JAK2,and STAT3 In The Lungs Of Rats

Objectives:The study was designed to observe the expression of IL-6,JAK2 and STAT3 of rats with bleomycin-induced pulmonary fibrosis and the effect of the Exogenous hydrogen sulfide on them,to explore the molecular biological mechanisms of the Exogenous hydrogen sulfide on pulmonary fibrosis.Methods:60 Healthy female SD rats of 6-week-old were divided into four groups by random number table,each group of 15,they were normal control group?A?,bleomycin group?B?,BLM+Sodium hydro-sulfide?the H₂S donor?group?C?,BLM+prednisone acetate group?D?.The lung fibrosis model was established by intraracheal lavage of bleomycin(5mg.kg^-1)in group of B,C,and D,the rats in group A were treated with the same volume of normal saline by intratracheal instillation.the rats in group C and D were respectively treated with NaHS?28?mol/kg.d?by intraperitoneal injection and prednisone(0.56mg.kg^-1.d^-1)by gastric gavage,group A and group B were given equal volume of saline (10ml.kg^-1.d^-1)one day after bleomycin.Five rats were randomly sacrificed in each group at 7,14,and 28 days after perfusion of bleomycin or saline.The changes of alveolitis and pulmonary fibrosis were observed by microscopy through hematoxylin-eosin?HE?and Masson staining.The expressions of IL-6,JAK2,STAT3 protein and mRNA was observed using immunohistochemistry and then determined using real-time polymerase chain reaction?RT-PCR?.Results:?Pulmonary histopathological findings were consistent with the typical manifestations of pulmonary fibrosis confirmed the success of modeling;The pathological results of the lung tissues showed that the structure of rat lung tissue in control group was clear and complete,without fibrosis changes and interstitial inflammation such as obvious congestion,exudation and edema at 7,14,and 28 days;There were more inflammatory cell infiltration in group B,thickened alveolar septa and few fibroblast proliferation were also observed on the 7th day;On the 14th day,the degree of alveolitis and inflammatory cell infiltration in lung tissue was reduced,the alveolar septum was increased noticeably and the proliferation of fibroblasts was more obvious than before;On the28th day,alveolar cavity had collapsed or disappeared within a large number of collagen deposition and tremendous proliferation of fibroblasts,multiple fibrous nodules were seen on the surface of lung tissue,Indicating that the rat pulmonary fibrosis model has been successfully established;The changes of lung tissues in group C and group D were similar to those of fibrosis group,but the focal hemorrhage and nodule of lung surface were less than that of fibrosis group,and the lung tissue texture soft,Compared with the fibrotic group,the number of inflammatory cells decreased in group C and group D on the 7th day and the 14th day,and the degree of pulmonary fibrosis at the corresponding time point was also lighter than that in the pulmonary fibrosis group.?Immunohistochemistry and RT-PCR showed:In group A,IL-6,JAK2,and STAT3 were lowly expressed at each time;The expression of IL-6,JAK2,and STAT3 in lung tissues of B,C,and D groups was significantly higher than that of A group at the same time point?P<0.05?,peaked at day7 and then decreased,but the expression was still higher than that in the control group at day 28?P<0.05?;The expression of IL-6,JAK2,STAT3in group C and group D was lower than that in group B at each time point,the difference was statistically significant?P<0.05?;The difference expression of IL-6,JAK2,and STAT3 in group C and group D had no significant difference?P>0.05?.Conclusion:The inhibition of IL-6,JAK2 and STAT3 by exogenous hydrogen sulfide may be related to the mechanism of anti-pulmonary fibrosis.