| Objective: The study was designed to observe influence effects of simvastatin onlung tissue angiogenesis and the gene expression of vascular endothelial growthfactor(VEGF) and platelet factor4(PF4) of rats with bleomycin (BLM)-inducedpulmonary fibrosis, to explore the molecular biological mechanisms of simvastatinused to treat pulmonary fibrosis, to find a theoretical basis for simvastatin’s clinicalapplications.Methods:96Healthy male SD rats of6-week-old were divided into four groups byrandom number table.They were normal control group (A), bleomycin group(B),prednisone acetate treatment group (C), simvastatin treatment group (D). Group B,group C and group D were5mg/kg single intratracheal dose of bleomycin toestablish an animal model of pulmonary fibrosis. Group A was intratracheal injectedsame amount of saline. Group C, group D were respectively gavaged5mg/kgprednisone suspension,10mg/kg simvastatin one day after the administration ofbleomycin. Group A and group B were respectively gavaged daily an equal amount ofsaline.Rats in each group were drawn3times after modeling7days,14days,28days,each time8rats were killed randomly in each group, a total of32. Alveolitis andpulmonary fibrosis changes were observed by using lung tissue HE staining.Angiogenesis, VEGF and PF4protein expression in lung tissue of rats in each groupwere determined by using immunohistochemical method (SP). Expression of VEGFand PF4mRNA in lung tissue were respectively detected by using RT-PCR assay.Results:①T he lung histopathology results showed that in A group lung tissuestructure was clear and complete,no congestion, edema, exudates and no fibroticlesions. On the7th day the B group showed mild alveolitis, alveolar septa widened,more inflammatory cell infiltration, visible fibroblasts;On the14th day alveolitispeaked, alveolar septa widened significantly, inflammatory cell infiltration aggravated, fibroblasts proliferated significantly;On the28th day pulmonary fibrosis becameobvious, alveolar space collapsed or disappeared, fibroblast proliferated in abundance,a large number of collagen deposition were visible.Compared with the model group,the hormone and simvastatin treatment group have varying degrees of ease inalveolitis and fibrosis in the corresponding point in time.②Comparison betweengroups at same point in time: lung tissue microvascular density (MVD) in B, C groupare higher than in group A, the difference was statistically significant; the differencebetween B, C two groups was not statistically significant. microvessel density ingroup D was significantly lower than group B, the difference was statisticallysignificant.③Immunohistochemistry and RT-PCR results: comparison between eachgroup at same point in time, VEGF expression in lung tissue of group B, C wassignificantly higher than that in group A, the difference was statistically significant;comparison between B and C groups showed no statistically significance; VEGFexpression in lung tissue of group D was significantly lower than that in group B, thedifference was statistically significant. PF4expression in lung tissue of Group B andgroup C was significantly lower than that in group A, the difference was statisticallysignificant; comparison between the B, C groups showed no significant difference;PF4expression in lung tissue of group D was significantly higher than that in group B,the difference was statistically significant.Conclusions:①simvastatin is able to inhibit pulmonary fibrosis neovascularization,mitigate the degree of alveolitis and pulmonary fibrosis.②Mechanism of simvastatinagainst lung fibrosis may be related to inhibition of VEGF expression, relativeincrease of PF4expression, inhibition of pathological angiogenesis in lungtissue,③Glucocorticoid can not lessen lung tissue angiogenesis in pulmonary fibrosis. |
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