Therapeutical Effect Of Recombinant Cytoglobin On The Rat Models With Pulmonary Fibrosis Induced By Bleomycin

Background:Idiopathic pulmonary fibrosis(idiopathic pulmonary fibrosis,IPF)is a kind of unknown etiology,with ordinary interstitial pneumonia as the characteristic pathological changes of a chronic fibrosis,interstitial lung disease.IPF prognosis,the median survival period for 3 years after the diagnosis,the 5-year survival rate is close to 20%,that the case fatality rate is higher than part of IPF cancer! Because of unknown etiology,therefore IPF is lack of effective treatments.Hormone is a useful drug for the treatment of IPF,but the long-term use of hormone can lead to immunosuppression,infection,hemorrhage,and severe adverse reactions.Therefore,to explore a safe and effective IPF therapy new is around the corner!RCygb(Cytoglobin Cygb)is a newly discovered including heme prosthetic group of six ligand globulin,current study found Cygb with prevention of liver fibrosis,realizing the function of the liver fibrosis reversal.Our success in previous experiments have established rhCygb double sandwich ELISA method,the test can successfully detect Cygb in serum of rats;Successful build of the different degree of liver fibrosis model,can be used in animal models of liver fibrosis research;Cells,relative to the liver fibrosis,four globin change can reflect the different degree of liver fibrosis,can be used as diagnostic indicators of liver fibrosis.On the basis of the above work,we suspect CYGB may be effective for the treatment of IPF animal model and to carry out this study.Objective:To study the CYGB of IPF rat model of pulmonary CT imaging and pathological change,the influence of four and CYGB fibrosis and the effects of the hydroxyproline content in lung tissue.Methods:45 SPF only adult male SD rats were randomly divided into normal group and 11(group a)and build module 34.Using endotracheal 5 mg/kg bleomycin injection approach to build model.In 7 days after the building of all rats after anesthesia with chest CT scan to determine whether building success.Confirm the building after a successful build model rats were randomly divided into model group(group b,n =11),dexamethasone treatment group(group c,n = 11)and CYGB group(d group,n =12).B group was given common breeding,don't give any drug intervention;Since 7 days after building group c daily subcutaneous injection of dexamethasone injection 3 mg/kg;Group d since 7 days after building daily subcutaneously CYGB solution 4 mg/kg.Respectively after building the 28 d and 56 d of rat tail vein blood,luminescence immune method is used to detect hyaluronidase(HA),laminin(LN),type ? before collagen(P ? P)and collagen type IV IV(C)content;After building 56 d of the secondary pulmonary CT scan in rats,then put to death all the rats,lung pathology Masson trichromatic dyeing;Using basic hydrolysis method method to detect hydroxyproline(HYP)content.Using single factor analysis of variance,repetitive measure analysis of variance and rank and inspection and other statistical methods,is more than 4 the index set of changes.Results:1.CT scanning:7 d after building with chest CT scan,found a model in rat lung to appear different degree of fibrosis changes,abnormal lung consolidation,blood vessels,bronchial beam section,interface irregular thickening,chest,grinding glass sample density,nodular shadows,honeycombing part of rat;According to the imaging changes the most typical interest area(ROI),measuring the CT value,found that build module CT average-(535.78 +/-165.94)Hu,significantly higher than that of normal group-(705.29 + 236.82)Hu(P<0.05),the above shows that building has been in line with the imaging of pulmonary fibrosis in rats changes,suggests building success.In the 56 d,four groups of lung CT value exists significant difference,in group d rats was significantly lower than the other three groups(P<0.05).2.Fibrosis:Compared with group a,building modules of HA,LN,P ? P and C IV levels were significantly higher(P<0.05).Group c and d in the treatment of 28 and 56 d of the above four levels were significantly lower than before the treatment,and significantly lower than that of group b(P<0.05);Comparison between groups showed in the treatment of 28 and 56 d,c and group d were no statistical difference of HA,LN and IV c,d group had a significantly lower than that of group c P ? P(P<0.05).3.Masson trichromatic pathological dyeing:compared with group a,b,c and group d dyeing score increased significantly(P<0.05);C and group d score after treatment was significantly lower than group b(P<0.05),significantly lower than that of group c and group d(P<0.05).4.HYP content:compared with group a,b,c and d groups of HYP content increased significantly(P<0.05);C and d groups of HYP content after treatment was significantly lower than group b(P<0.05),significantly lower than that of group c and group d(P<0.05).Conclusion:1.rCygb can significantly reduce the bleomycin induced pulmonary fibrosis in rats peripheral blood fibrosis indexes,significantly improve bleomycin induced pulmonary fibrosis in rats chest CT imaging changes,significantly reduce bleomycin induced lung hydroxyproline content in the organization,significantly improve bleomycin induced lung tissue pathology change.2.Compared with dexamethasone,in improving peripheral blood rCygbhyaluronidase,laminin,and collagen type ?(no statistical difference,but in front of the lower type ? collagen effect,bead cell protein is superior to dexamethasone.3.Dexamethasone and rCygbin chest CT imaging changes in the rat model of pulmonary fibrosis no statistical difference.4.rCygb reduce effect of hydroxyproline content in the lung tissue is superior to dexamethasone.5.rCygb is expected to be a new drug for the treatment of pulmonary fibrosis.