Mechanism of action of dexamethasone on expression of T-bet?GATA-3 and airway inflammation in asthmatic rats
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    Abstract:

    Objective:To observe the effect of dexamethasone on expression of airway inflammation and transcription factor T-bet and GATA-3 in asthmatic rats. Methods:Thirty-six SD rats(SPF) were randomly divided into normal control group(group A),asthmatic model group(group B) and dexamethasone group(group C) with 12 rats in each group. The asthmatic model of SD rats was established by immunization with intraperitoneal injected and inhaled ovalbumin(OVA). The animals were executed under anesthesia within 24 h after the last atomization. The morphological changes in lung tissues of rats were measured. The thickness of airway wall(WA/Pi) and airway smooth muscle(ASM/Pi),and the numbers of eosinophils and lymphocytes were measured. The concentrations of interleukin-2(IL-2),IL-4,IL-5 and interferon-γ(IFN-γ)in bronchoalveolar lavage fluid(BALF) were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein expressions of T-bet and GATA-3 in the lungs were measured semiquantitatively by reverse transcription-polymerase chain reaction(RT-PCR) and Western blotting, respectively. Results:In group B and group C,the numbers of eosinophils and lymphocytes,and the WA/Pi and ASM/Pi were all significantly higher than those in group A(P < 0.01). The four indexes in group C were all significantly lower than those in group B(P < 0.01). In group B and group C,the concentrations of IL-4 and IL-5 in BALF were all significantly higher than those group A(P < 0.01),the concentrations of IL-2 and IFN-γ in BALF were all significantly lower than those in group A(P < 0.01). In group C,the concentrations of IL-4 and IL-5 in BALF were all significantly lower than those group B(P < 0.01),but the concentrations of IL-2 and IFN-γ in BALF were no significantly than those in group B. In group B and group C,expressions of T-bet were significantly lower than that in group A(P < 0.01),but expressions of T-bet in group C were no significantly than that in group B. In group B and group C,expression of GATA-3 were significantly higher than that in group A(P < 0.01). Expression of GATA-3 in group C were significantly lower than that in group B(P < 0.01). The correlation analysis indicated that in group B,protein expressions of T-bet was negatively correlated with the numbers of eosinophils and lymphocytes,and the WA/Pi and ASM/Pi(r = -0.82,-0.86,-0.78,-0.80,P < 0.01),But protein expression of GATA-3 was positively correlated with the numbers of eosinophils and lymphocytes,and the and ASM/Pi(r = 0.83,0.85,0.76,0.79,P < 0.01). Protein expression of T-bet was negatively correlated with protein expression of GATA-3 in group B(r = -0.88,P < 0.01). Conclusion:The expressions of T-bet were low in bronchial asthmatic rats,and the expressions of GATA-3 were high in bronchial asthmatic rats. Dexamethasone can lessen airway inflammation and expression of GATA-3,but there was no significant effect on expression of T-bet with dexamethasone.

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吉宁飞,周玉婷,何 畏,卞 涛,殷凯生.地塞米松对哮喘大鼠T-bet?GATA-3及气道炎症的作用机制[J].南京医科大学学报(自然科学版英文版),2008,28(11):1421-.

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