糖皮质激素对哮喘豚鼠模型Eotaxin、CCR3表达的调控

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目的:观察哮喘豚鼠外周血、肺和骨髓组织嗜酸性粒细胞(EOS)百分比和肺组织Eotaxin和CCR3的表达及激素对其影响。方法:健康雄性豚鼠40只,以卵白蛋白(OVA)致敏和激发制作哮喘模型,随机分为正常组(A组)、哮喘组(B组)、地塞米松干预组(C组)、布地奈德干预组(D组),每组10只,在末次激发6h后处死豚鼠;取豚鼠颈动脉血、骨髓和肺组织,分别制备血涂片、骨髓涂片和肺组织切片;外周血和骨髓涂片用Wright染色,光学显微镜下计数细胞总数和EOS百分比;肺组织切片HE染色,光学显微镜下计数细胞总数和EOS百分比;肺组织切片用Eotaxin和CCR3多克隆抗体免疫组化染色,光学显微镜下分别计数阳性细胞百分比;用Westernblot法测定肺组织中Eotaxin蛋白表达变化。结果:豚鼠外周血、骨髓和肺组织中EOS百分比,A组为(1.33±0.52)%、(1.17±0.41)%、(1.67±0.52)%;B组为(4.83±0.98)%、(3.17±0.75)%、(4.00±0.89)%;C组为(2.68±1.03)%、(1.67±0.82)%、(2.83±0.75)%;D组为(2.67±0.52)%、(1.83±0.75)%、(2.67±0.52)%;B组与A、C、D组比较差异有统计学意义(P<0.05),A组与C、D组比较差异有统计学意义(P<0.05),C组与D组比较差异无统计学意义(P>0.05),但C组较D组降低骨髓EOS百分比似乎更明显;豚鼠肺组织Eotaxin和CCR3多克隆抗体免疫组化染色阳性细胞百分比,A组为(2.29±0.35)%、(2.07±0.15)%;B组为(3.27±0.42)%、(3.66±0.47)%;C组为(2.80±0.22)%、(2.98±0.45)%;D组为(2.75±0.31)%、(2.65±0.25)%;B组与A、C、D组比较差异有统计学意义(P<0.05),A组与C、D组比较差异有统计学意义(P<0.05),C组与D组比较差异无统计学意义;免疫印迹法检测发现豚鼠肺组织Eotaxin在A、B、C、D组表达量分别为0.447±0.026、0.836±0.012、0.639±0.034、0.668±0.023,B组表达较A、C和D组明显升高(P<0.01),C组与D组比较差异无统计学意义,但仍高于A组(P<0.05);相关性分析结果提示哮喘豚鼠肺组织中EOS百分比和Eotaxin和CCR3在肺组织的表达皆呈正相关(r=0.852,P<0.001)、(r=0.671,P<0.001)。结论:哮喘豚鼠外周血、骨髓和肺组织EOS均明显增加,并与肺内Eotaxin和CCR3的表达相一致,激素可通过抑制Eotaxin和CCR3的表达和活性,有效发挥抗EOS炎症作用,是激素控制哮喘发病的重要机制。 OBJECTIVE: To observe the percentage of eosinophils (EOS) in peripheral blood, lung and bone marrow of asthmatic guinea pigs and the expression of Eotaxin and CCR3 in lung tissue and the effects of hormones on them. Methods: Forty male guinea pigs were sensitized and challenged with ovalbumin (OVA) to establish a model of asthma. They were randomly divided into normal group (group A), asthma group (group B), dexamethasone intervention group (group C) (Group D), with 10 rats in each group. Guinea pigs were sacrificed 6 hours after the last challenge. Blood samples of the guinea pigs, bone marrow and lungs were obtained from the carotid blood, bone marrow and lung tissues of guinea pigs. Blood and bone marrow The smears were stained with Wright and the total number of cells and the percentage of EOS were counted under optical microscope. The sections of lung were stained with HE, the total number of cells and percentage of EOS were counted under light microscope. The sections of lung were stained with Eotaxin and CCR3 polyclonal antibody by immunohistochemistry. The percentage of positive cells was counted respectively. The expression of Eotaxin protein in lung tissue was detected by Western blot. Results: The percentage of EOS in guinea pigs was (1.33 ± 0.52)%, (1.17 ± 0.41)% and (1.67 ± 0.52)% respectively in group A, (4.83 ± 0.98)% and (2.67 ± 0.52)%, (1.83 ± 0.75)% in group D and (2.83 ± 0.75)% in group C ), (2.67 ± 0.52)%, respectively. There was significant difference between group B and groups A, C and D (P <0.05). There was significant difference between group A and group C and D (P <0.05) There was no significant difference between group C and group D (P> 0.05), but the percentage of EOS in group C was lower than that of group D. The percentage of Eotaxin and CCR3 polyclonal antibody in guinea pig lung was higher (2.29 ± 0.35)% and (2.07 ± 0.15)% in group B, (3.27 ± 0.42)% and (3.66 ± 0.47)% in group B, and 2.80 ± 0.22 and 2.98 ± 0.45 respectively in group C (2.75 ± 0.31)%, (2.65 ± 0.25)% in group B, which were significantly different from those in group A, C and D (P <0.05). The difference between group A and group C and group D was statistically significant (P <0.05). There was no significant difference between group C and group D. The expression of Eotaxin in group A, B, C and D in guinea pig lung was 0.447 ± 0.026,0.836 ± 0.012,0.639 ± 0.03 4,0.668 ± 0.023. The expression of B group was significantly higher than that of A, C and D groups (P <0.01), but there was no significant difference between C group and D group (P <0.05) The results of sex analysis suggested that the percentage of EOS in the lung tissue of asthmatic guinea pigs was positively correlated with the expression of Eotaxin and CCR3 in lung tissues (r = 0.852, P <0.001) (r = 0.671, P <0.001). CONCLUSIONS: The EOS of peripheral blood, bone marrow and lung of asthmatic guinea pigs were significantly increased and consistent with the expression of Eotaxin and CCR3 in lung. The hormones can exert anti-EOS inflammatory effect by inhibiting the expression and activity of Eotaxin and CCR3 and are hormone control An important mechanism of asthma.
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