| BackgroundPulmonary fibrosis is a group of diseases of lung damage caused by multiple causes,but the pathogenesis is unclear now.The Pathologic process of pulmonary fibrosis is when the lung tissue after damage by physical,chemical,harmful biological factors,fibroblasts respond to stimulation,synthesis and secretion a lot of collagen to repair the damaged lung tissue,make collagen and extracellular matrix(ECM)excessive deposit in lung interstitium,causing pulmonary fibrosis,accompanied by transforming growth factor-?(TGF-p),increased expression of inflammatory factors.MicroRNAs(miRNAs)are a group of endogenous single strand of small non-coding RNA molecules,widely found in eukaryotic cells.MicroRNAs is involved in many physiological and pathological processes of the cells or tissues of regulation,it plays an important role in cell differentiation,proliferation,apoptosis and tissue and organ development,metabolism and other processes.A variety of research have confirmed miRNAs are involved in cancer,autoimmune diseases and other systemic diseases development.Numerous studies show that there are several miRNAs abnormal expression in fibrosis diseases,and some aberrant expression of miRNAs is closely related to the development of fibrotic disease.So further Study the role of these miRNAs in the pathogenesis of fibrotic disease mechanisms become current research focus.MiR-21 plays an important role in the pathogenesis of fibrotic disease.Some studies show that the expression of miR-21 is up regulated in fibroblasts by TGF-?1-induced pulmonary fibrosis in lung fibroblasts in vitro models.MiR-21 express upgrate in lung fibroblasts induced by TGF-?1 upgrate expression of miR-21 can be further enhanced profibrotic effect of TGF-?1 within the cells,make fibroblast proliferation and activation,collagen excessive deposited,lead to fibrosis eventually,miR-21 amplifies the signal ofTGF-?3.Conversely,use anti-mir-21 to make miR-21 gene silencing,fibrosis effect of TGF-?1 is greatly reduced.Thus,miR-21 may be the potential targets of improve pulmonary fibrosis.This paper mainly discusses whether resveratrol(Res)by adjusting the miR-21 expression,regulation of pulmonary fibrosis of a key signaling molecule expression of TGF-?1,thereby intervene pulmonary fibrosis,to clear miR-21's role in the process of pulmonary fibrosis.Discuss miR-21 as a potential target for treatment of pulmonary fibrosis.ObjectivesTo investigate the role of miR-21 and TGF-?1 in the pathogenesis of bleomycin-induced pulmonary fibrosis,and to explore the effects of resveratrol on miR-21 and TGF-?1 expression.MethodSeventy male SD rats were randomly divided into control group(n=10),model group(n=30)and resveratrol group(n=30).Rats in the latter 2 groups were intratracheally administered with bleomycin to produce pulmonary fibrosis,whereas ones in control group were treated with same volume of normal saline.From the first day,rats in intervention group were intragastrically treated with 100 Mg/kg-1 Res,whereas ones in the other groups were treated with normal saline in the same condition.Ten rats in model and intervention groups were sacrificed on days 7,14 and 28 while all ones in control group were killed on day 28 as total control.Remove the pulmonary tissue under sterile conditions and save,HE staining andMasson staining were performed.The mRNA and protein expression of miR-21 and TGF-?1 was detected by fluorescence real time quantitative PCR and Western blotting respectively.Result1.HE/Masson Staining on the lung tissue HE Staining:There was no lesion of the lung innormal control group rats.In the model group,there were obvious alveolitis in the lung tissue,significant exudates of inflammatory cells from the alveolar and a small amount of collagen deposition in the pulmonary interstitial at the 7th day;the lung inflammation reduced,alveolar septum widened and fibroblasts hyperplasia,collagen deposition,alveolar space narrowing were seen at the 14th day;it formed stable pulmonary fibrosis,and some inflammatory cellswere observed at the 28th day.The resveratrol group had the same trends with the model group,but less than them.Masson staining:In the control group,the bronchial wall of lung tissue was thin and there was a small amount of collagen deposition in the interval of bronchial walls.In the model group,pulmonary interstitial,bronchial wall,and pulmonary interstitial collagen fibers were becoming more and more.At 7th day,the collagen fibers mainly distributed over around the bronchi and small blood vessels.There was no significant collagen fiber in alveolar septa;At 28th day,There were more collagen fibers around the bronchi and small blood vessels in the model group,a lot of pulmonary interstitial collagen fibers distributed as bundles and patches and even some of the alveolar spaces were filled with collagen fibers.The resveratrol group had the same trends with the model group,but less than them.2.The expression of TGF-?1 and TGF-?1 mRNA The expression of TGF-?1 at the gene and protein levels in the control group was low.The expression of TGF-?1 at the gene and protein levels in the model group and the resveratrol groups was more than that the control group(P<0.05).In the model group and the resveratrol groups the expression at each time point were significantly enhanced,but the Res group was significantly higher than the control group and lower than the model group,at each time point has significant difference compared with the normal group(P<0.05).3.The expression of miR-21 The expression of miR-21 in the control group was low.The expression of miR-21 in the model group and the resveratrol groups was more than that the control group(P<0.05).In the model group and the resveratrol groups the expression at each time point were significantly enhanced,but the Res group was significantly higher than the control group and lower than the model group,at each time point has significant difference compared with the normal group(P<0.05).Conclusion1.Resveratrol can reduce the degree of pulmonary fibrosis in rats.2.Resveratrol can reduce the expression of TGF-?1 at the gene and protein levels.3.Resveratrol can reduce the expression of miR-21.4.Resveratrol may downregulate the expression of miR-21 to improve TGF-?1 signal transduction pathway and its downstream effects,improving pulmonary fibrosis. |
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