ABSTRACT
Aim To study the effects of pyrin recombi-nant protein ( PRP ) on VEGF/VEGFR2/ MMP-9 sig-naling pathway in bleomycin-induced pulmonary fibro-sis of rats. Methods Sixty male Wistar rats were ran-domly divided into groups of control ( n=10 ) , model ( n=20 ) , PRP ( n=20 ) , and SU5416 ( n=10 ) . All the rats, except for those in control group, were estab-lished as the model of interstitial pulmonary fibrosis by perfusion of bleomycin (5 mg·kg-1 ) through tracheal intubation. From the second day after modeling, all rats were intragastrically administered with drugs or sa-line, according to different groups designed. The rats were sacrificed on the 14th and 28th day, and lung samples were taken out. The pathological changes of interstitial pulmonary fibrosis were observed by HE staining and Masson staining to evaluate the degree of alveolitis and pulmonary fibrosis. Expressions of VEGF, VEGFR2, MMP-9 protein and mRNA were de-tected by immunohistochemistry and RT-PCR. Results On the 14th and 28th day, the alveolitis, pulmonary fibrosis, expression of VEGF, VEGFR2, MMP-9 and mRNA increased significantly in the model group com-pared with in the control group ( P <0. 05 ) , and de-creased significantly in PRP group than those in the model group ( P <0. 05 ) . Conclusion PRP plays a role of anti-pulmonary fibrosis via the down-regulation of VEGF/VEGFR2/MMP-9 signaling pathway.
ABSTRACT
Aim To investigate the effects of sesamin on inflammation response of asthma and to explore its possible mechanism of action. Methods Forty male BALB/c mice were randomly divided into five groups with 8 mice in each group: normal group, ovalbumin ( OVA) group, sesamin low dose group, sesamin high dose group and dexamethasone( DXM) group. Asthma model mice were induced by OVA in vivo. The left lung was isolated for pathological examination. Experi-ment of ELISA and Western blot were used to deter-mine the effect of sesamin on IL-4 , IL-5 , IL-13 and IFN-γ expression. Hematoxylin and eosin stain was used to investigate pathological examination in lung tis-sue. Western blot was performed to detect the IκBαphosphorylation and NF-κB nuclear translocation. Re-sults The mice developed the following pathophysio-logical features of asthma: increased numbers of in-flammatory cells, increased levels of IL-4, IL-5 and IL-13 , decreased level of IFN-γ in bronchoalveolar lavage fluids ( BALF ) and lung tissues ( P <0. 05 ) , and increased IκBα phosphorylation and NF-κB nucle-ar translocation in lung tissues ( P <0. 05 ) . Adminis-tration of sesamin markedly reduced airway inflammato-ry cell recruitment, reduced the production of IL-4, IL-5 , IL-13 and increased IFN-γ in BALF and lung tissues( P <0. 05 ) . The increased IκBα phosphoryla-tion and NF-κB nuclear translocation after OVA inhala-tion were inhibited by the administration of sesamin. Conclusion Sesamin attenuates inflammation re-sponse of asthma through suppression of NF-κB activa-tion.
ABSTRACT
Objective To investigate the blocking effects of Pyrin domain protein on mouse allergic airway inflammation induced by ovalbumin and its mechanism.Methods Forty male BALB/c mice were randomly divided into 4 groups with 10 mice in each group.Control group:mice were treated with saline;OVA group:mice were sensitized and challenged with OVA; Pyrin domain protein 3 d group:mice were sensitized and challenged as asthmatic group and treated with 100 μg/kg triptolide before challenged; Pyrin domain protein 7 d group:mice were sensitized and challenged as asthmatic group and treated with 100 μg/kg triptolide before challenged.All mice were killed 24 h after final OVA challenge.The left lung was isolated for pathological examination.Lung sections were stained with hematoxylin and eosin(HE),Masson's trichrome.The thickness of bronchial airway,bronchial smooth muscle thickness,and the collagen deposition area were measured by image analysig system.The concentrations of IL-4,IL-5,TNF-α and IFN-γ in BALF were measured by ELISA,the RT-PCR and Western blot was performed to detect the mRNA expression of connective tissue growth factor (CTGF),TGF-β 1 mRNA and NF -kB from the right lung tissues.Results In OVA group,the number of inflammatory cells and the concentrations of IL-4,IL-5,TNF-a in BALF and Bronchial airway thickness,bronchial smooth muscle thickness,the collagen deposition area,CTGF,TGF-β1 mRNA and NF-kB in lung tissue were significantly higher than those in control group(P＜0.05).IFN-γ were lower than those in control group( P＜0.05 ).While in Pyrin domain protein 3 d group and Pyrin domain protein 7 d group,the number of inflammatory cells,the concentrations of IL-4,IL-5,TNF-α in BALF and bronchial airway thickness,bronchial smooth muscle thickness,the collagen deposition area and NF-kB in lung tissue were significantly lower than those in OVA group,IFN-γwere higher than those in OVA group( P ＜0.05).In Pyrin domain protein 7 d group CTGF and TGF-β1 mRNA in lung tissue were significantly lower than those in OVA group.Conclusion Pyrin domain protein might inhibits airway inflammation and development of airway remodeling in asthmatic mouse,the possible mechanism might in part by associated with reducing the expression of NF-kB and further inhibiting CTGF,TGF-β1.