| Research BackgroundPulmonary fibrosis is a disease characterized by pulmonary structural lesions,which is the result of abnormal repair of normal alveolar tissue in the event of injury.When the lung tissue is damaged,a slight inflammatory response occurs and is then secreted Collagen repair of lung interstitial tissue,if the alveolar exudate and debris can not be effectively cleared,it will lead to interstitial fibroblasts hyperplasia,resulting in a large number of collagen and extracellular matrix,A large number of deposition of the external matrix will lead to alveolar wall,airway and vascular scar fibrosis.MicroRNAs(miRNAs)are widely involved in the regulation of physiological and pathological processes in the tissues and cells of the organism,and are closely related to the process of cell proliferation,diff-erentiation,apoptosis regulation,tissue organ development and metabolism.Studies have confirmed that miRNAs are widely involved in the development of tumors,autoimmune diseases and other systemic diseases and play an important role in a variety of diseases.Studies have shown that miR-21 plays an important role in the pathogenesis of pulmonary fibrosis.Nuclear factor ?B(NF-?B)is a nuclear transcrption factor closely related to inflammatory cytokines,which regulates the expression of many inflammatory cytokines mRNA,which is closely related to inflammatory diseases.NF-?B activates inflammatory cytokines TNF-? and IL-1?,causes alveolitis,and induces TGF-?,activates TGF-?/Smad signaling pathway,causes collagen secretion,leading to pulmonary fibrosis.In this study,we established the model of pulmonary fibrosis and treated resveratrol to study the effect of resveratrol on pulmonary fibrosis.The effects of resveratrol on miR-21 and NF-?B were studied,The mechanism of alcohol in the process of interventional pulmonary fibrosis.ObjectiveTo study the effect of resveratrol on pulmonary fibrosis and the effect of resveratrol on miR-21 and NF-?B expression.Method90 male SD rats were randomly divided into 4 groups(n = 30),normal control group(group A),pulmonary fibrosis model group(group B)and lung fibrosis Resveratrol intervention group(group C).Group A was not modeled,model group B group and intervention group C group were tracheal injection of bleomycin method to establish the establishment of pulmonary fibrosis model After treatment,group A and group B were given normal saline.Group C was given resveratrol and given 10 rats at 7 days,14 days and 28 days Detection.Result1.The general observation of lung tissue the normal control group lung surface smooth,no bleeding point.In the model group,the lung volume was increased on the 7th day,and the bleeding was on the surface.The bleeding was increased on the 14th day,and the local tissue structure changed nodular.The size was reduced on the 28th day,the color became pale,the local consolidation and the surface The structure of the groove changes.Resveratrol intervention group:the first 7 days when the lung volume has increased slightly,the surface visible bleeding;14 days of bleeding increased;28 days increased hardness,local nodular structure changes.2.Histopathological section HE staining and Masson staining It is showed that the normal lung tissue of the control group was normal,the alveoli was full,the alveolar cavity shape was the same,the size of the alveolar wall was thin and no inflammatory cell infiltration was found.On the 7th day,the alveolar septum was observed in some areas.Inflammatory cell infiltration,inflammatory foci formation,fibroblast hyperplasia,partial alveolar enlargement and collapse were observed.On the 14th day,the alveolar structure was damaged,the alveolar cavity was irregular,the alveolar septum was widened,but the infiltration of inflammatory cells decreased and the fibroblasts increased obviously.At the 28th day,the alveolar structure was seriously damaged,some alveoli disappeared,showed positive changes,inflammatory cell infiltration was significantly reduced,fibroblasts proliferation,local lung tissue into honeycomb-like changes;resveratrol intervention group:similar to the model group The pathological changes of lung tissue were significantly decreased in the resveratrol group at different time points compared with the model group.Masson staining showed that the bronchial wall of the normal control group showed no blue-stained fibrous tissue,alveolar and interstitial blue fibrous fibrous tissue deposition.In the model group,a small amount of blue staining was observed on the 7th day Of the fibrous tissue deposition,mainly distributed in the bronchus and small blood vessels around the alveolar interval widened.On the 14th day,the deposition of collagen fibers around the bronchus was significantly increased,and the alveolar septum was further widened,and more collagen fibers were deposited.The resection of resveratrol in the lung tissue was similar to that in the model group.However,the histopathological changes of the lung tissue in the resveratrol group at each time point and the model group Compared with the same period significantly reduced.3.Hydroxyproline content in the normal control group,the content of hydroxyproline in almost no change;the group at each time point of the hydroxyproline content were significantly higher than the normal group,with the passage of time,hydroxyproline(P<0.05).The content of acid was increased at 28 days,and there was significant difference compared with normal control group(P<0.05).In the treatment group of resveratrol intervention group,The trend of acid content was similar to that of model group,and reached the maximum at 28 days.The resveratrol intervention group was significantly lower than that of model group.4.The results of Western blotting showed that NF-?B P65 protein was weakly expressed in the normal control group.The protein of NF-?B P65 at the 7th day,14th day and 28th day of the model group The expression level of NF-?B P65 protein reached the maximum at day 7,and the expression of NF-?B P65 protein reached the maximum at the 14th day and 28th day The protein expression level of NF-?B P65 in resveratrol intervention group was significantly higher than that in normal control group at different time points,and the protein expression level of NF-kB P65 was significantly higher than that of normal control group The model group was consistent,all reached the maxmum on the 7th day,then the 14th day,the 28th showed a decreasing trend.However,the expression level of NF-?B P65 protein in resveratrol group was significantly lower than that in model group(P<0.05).5.The expression of miR-21 in the model group was significantly higher than that in the normal control group,and the expression level of miR-21 reached the maximum at the 7th day,but the expression of miR-21 was higher than that of the normal control group The expression of miR-21 in the resveratrol-treated group showed a decreasing trend with the model group,but the trend of the expression of miR-21 was significantly lower than that of the model group(P<0.05).The expression of type I collagen mRNA in the model group was significantly higher than that in the normal control group,but the expression of type I collagen mRNA increased gradually with the passage of time.Type collagen mRNA expression in the resveratrol group was significantly higher than that in the normal control group at different time points in the resveratrol intervention group,and the expression of type I collagen mRNA was significantly higher than that of the model group The expression of type III collagen mRNA in the model group was significantly higher than that in the normal control group.The expression of type III collagen mRNA reached the maximum at day 7,but on the 14th day and the 28th day,The expression of collagen mRNA was The expression of type ?collagen mRNA in resveratrol group was significantly higher than that in normal control group at 7 days,14 days and 28 days at each time point,and the expression of type ?collagen mRNA was significantly higher than that of model Group compared with a significant reduction.Conclusion1.Resveratrol has a certain effect on bleomycin-induced pulmonary fibrosis in rats.2.Resveratrol inhibited the expression of miR-21 and NF-?B protein.3.The mechanism of resveratrol to improve pulmonary fibrosis may be by down-regulating miR-21 and NF-?B to reduce the deposition of collagen,and ultimately achieve the mitigation of fibrosis. |
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