| Objective：Pulmonary fibrosis is a complex disease based on a largenumber of fibroblast aggregation and deposition of extracellular matrix andassociated with inflammation and tissue destruction which are the mainfeature. It has many types including interstitial idiopathic pulmonary fibrosis(IPF), pneumoconiosis, hypersensitivity pneumonitis, sarcoidosis,radiation and drug-induced pulmonary fibrosis and fibrosis caused by collagenvascular disease. Idiopathic pulmonary fibrosis is the most commoninterstitial lung disease which is an immune-mediated inflammatory diseases,a variety of cytokines and inflammatory cells involved in its pathogenesis. Themost important means of clinical treatment is hormones and an immun-osuppressants,the mortality is very high due to the lack of special treatment.Currently looking for a more effective treatment is imminent. Thalidomide asa new type of drug widely used in clinical, the study found that it hasanti-inflammatory, anti-ang-iogenic and immunomodulatory effects. Itsanti-inflammatory effects be able to reduce the level of TNF-α in vivo, at thesame time be able to inhibit the generation of PDGF reduce angiogenesis.These effects of thalidomide may be closely related to the inhibition ofpulmonary fibrosis.The purpose of this experiment is to study the role of the thalidomide anddexamethasone to treat the fibrosis caused by bleomycin. By measuring theserum expression levels of TNF–α，PDGF and lung tissue collagen content,explore the possible mechanism of action.Method：Election of clean healthy male SD rats，72，provided by theExperimental Animal Center of Hebei Medical University，weight250-300g，the adaptability feeding after a week，randomly divided into：(1) groupA(Control group)：18rats,each subgroup6rats, the rats injected about normal saline (0.1ml/100g) in trachea for slowly and after fake establishingmodel, the rats were given intragastric administration with normal saline(1ml/100g) once a time per day, then were killed randomly on the7thday,the14thday, the28thday each subgroup6rats.(2) group B (model group):18rats,each subgroup6rats, Pumlonary fibrosis was induced by intratrachealinjection of Bleomycin A5(5mg/kg).After establishing model, the rats weregiven intragastric administration with normal saline (1ml/100g) once a timeper day, then were killed randomly on the on the7thday,the14thday, the28thday,each subgroup6rats.(3) group C (thalidomide group)18rats,eachsubgroup6rats, the rats were injected Bleomycin A5(5mg/kg) in trachea forslowly and after establishing model were treated with thalidomide solution (1gof thalidomide dissolved in100ml of normal saline)100mg/kg once a timeper day, then were killed randomly on the7thday, the14thday and the28thday,each subgroup6rats.(4) group D (dexamethasone group):18rats, eachsubgroup6rats, the rats were injected Bleomycin A5(5mg/kg) in trachea, andafter establishing model were treated with dexamethasone solution（0.3mg/100g/d）, then were killed randomly on the7th day, the14th day andthe28th day, each subgroup6rats. Separate every rat bilateral femoral artery,during the operation to minimize the stimulation of the femoral artery, Afterfreed the femoral artery cut bilateral femoral artery, pressing the heart,collected the blood,by ELISA (enzyme-linked immunosorbent assay) methodfor the determination of content of rat serum TNF-α, PDGF. To freed andremoved the rat right lung, after this it was placed into and fixed in4%paraformaldehyde solution, understanding by measuring the averageintegrated optical density of the collagen content of collagen.Use HE andMasson staining method to evaluate the development of alveolitis and fibrosisof various lung tissue,based on Szapiel law,it can be divided into four level.Use SPSS13.0statistical software to analysis every data.Results:1The results of pulmonary pathology: Model group: at the same time the alveolitis in rat lung tissue wassignificantly higher than those in the control group (P<0.05), at the7day thelung fibrosis had no significant difference with control group (P>0.05),at the14day and28day, pulmonary fibrosis significantly compared with the controlgroup (P<0.05).Thalidomide group: This group of rats early alveolitis mainly overtime showed fibrosis. And at the7thday and14thday alveolitis comparedwith the control group heavier (P<0.05), but compared with the modelgroup mitigate (P<0.05); the28thdays with the control group and the modelgroup had no significant difference (P>0.05). at the7thday of pulmonaryfibrosis had no significant difference between the control group and themodel group (P>0.05), at the14thand28thday compared with the controlgroup heavier (P<0.05), at the14thday compared with model groupther hadno difference (P>0.05). at the28thday, compared with the model group thefibrosis reduced(P<0.05).Dexamethasone group: at the7thday and14thday alveolitis comparedwith the control group heavier (P<0.05), compared with the model group (P<0.05); at the28thday compared with the control group and the model grouphad no significant difference (P>0.05). at the7thday fibrosis compared withthe control group and the model group, there was no difference (P>0.05), atthe14thday compared with the control group heavier (P<0.05), comparedwith the model group no difference (P>0.05). at the28thday compared withthe control group no difference (P>0.05), significantly reduced (P<0.05) thanthe model group fibrosis.While we can not find the significant difference between dexamethasoneand thalidomide group on the same time point (P＞0.05).2The expression of type Ⅲ collagen in lung tissue (represented by theaverage optical density):Ⅲ collagen content of the model animals lung tissue gradually increasedover time amount to put to death the day up to a maximum value, comparedwith the control group there had a statistically significant (P<0.05). Thalidomide and dexamethasone group rat type III collagen content was slowgrowth trend, with the model group at each time point content were lower,with a statistically significant (P<0.05); at the7thday dexamethasone groupwith thalidomide group was not statistically significant (P>0.05), at the14thand the28thday of thalidomide the collagen amine group contentdexamethasone group was significantly lower, with a statistically significant(P<0.05).3The change of the content of TNF-α and PDGF in serum:The content of TNF-α in bleomycin group was significantly higher thanthe control group, there had a statistically significant (P<0.05), thalidomideand dexamethasone group campared with bleomycin rats the serum TNF-αlevels it was lower statistically significant (P<0.05) at the point each time. Atthe7thday the thalidomide group with dexamethasone group, compared with14days in serum TNF-α were significantly lower (P<0.05), at the28thday wasnot statistically significant (P>0.05).PDGF in the control group was significantly higher than bleomycingroup, it had a statistically significant (P<0.05).Thalidomide anddexamethasone group and each time point serum PDGF content its lower thanbleomycin rats (P<0.05) and the thalidomide group compared withdexamethasone in addition to at the28hday with a statistically significant (P<0.05) in the rest point in time was not statistically significant (P>0.05).Conclusions:1Bleomycin role in the rat can cause interstitial fibrosis in the rat lung.2Thalidomide and dexamethasone can reduce the content of collagenin bleomycin induced pulmonary fibrosis in rats.Thereby reducing the degreeof pulmonary fibrosis.3Thalidomide and dexamethasone can reduce the content of TNF-αand PDGF in rats serum, so as to reduce alveolar inflammation and furtherinhibit lung fibrosis.4The thalidomide and dexamethasone have a certain role in thetreatment of pulmonary fibrosis induced by bleomycin, however, there has no significant difference between the two. |
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