地塞米松对中性粒细胞性哮喘模型小鼠气道炎症的影响

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目的:观察地塞米松对中性粒细胞性哮喘(neutrophilic asthma,NA)模型小鼠气道炎症的影响。方法:C57BL雌性小鼠随机分成NA组、NA地塞米松干预(neutrophilic asthma treating with dexamethasone,NAD)组和正常(NC)组,每组8只。NA、NAD组予卵蛋白、脂多糖致敏并卵蛋白激发;NAD组激发前腹腔注射地塞米松;NC组不做处理。小鼠肺功能仪检测气道阻力,以阻力倍增值评价气道反应性;检测支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)有核细胞浓度及分类比例;流式细胞术检测脾脏Th17细胞及ki-67+Th17细胞比例;ELISA检测BALF IL-17浓度。结果(1)NA组气道阻力倍增值显著高于NC组(P<0.05)。(2) NAD组BALF有核细胞浓度、NEU%、EOS%均显著低于NA组,但仍高于NC组(均P<0.05)。(3)NAD组脾脏Th17细胞比例显著低于NA组,但仍高于NC组(均P<0.05);NA、NAD组脾脏ki-67+Th17细胞比例均显著高于NC组(均P<0.05),但NA、NAD组间差异无统计学意义。(4)NAD组BALF IL-17浓度显著低于NA组,但仍高于NC组(均P<0.05)。结论:地塞米松可能通过抑制Th17细胞及IL-17表达,减轻NA模型小鼠气道炎症;Th17细胞增殖功能增强且不受地塞米松影响可能与气道炎症持续存在有关。“,”Objective To observe the effect of dexamethasone on airway inflammation in the mouse model of Neutrophilic Asthma. Methods Female C57BL mice were randomly divided into NA, NAD and NC group.NA、NAD mice were sensitized by ovalbumin OVA and LPS and challenged by OVA. NAD mice were treated with dexamethasone at beginning of each challenge.NC mice without treatment.Airway resistance were measured and fold increase were caculated as an assessment for AHR.Total white blood cell concentration and classification of proportion were determined in the BALF.Percentages of Th17 cells and Ki-67+Th17 cells in the spleen were determined by FCM.BALF IL-17 concentration were determined by ELISA. Results (1) Fold increase of airway resistance in the NA group were higher than that of the NC group (each P<0.05).(2)BALF total cell count, neutrophil and eosinophil percentages in the NAD group were lower than that of the NA group (each P<0.05), but were higher than that of the NC group(each P<0.05). (3) Th17 cell percentages in the spleen of the NAD group were lower than that of the NA group, but were higher than that of the NC group(each P<0.05). Ki-67+Th17 cells percentage in the spleen of the NA and NAD group were higher than that of the NC group(each P<0.05);Hoever,no difference were found in the NA group compared with that of the NAD group(4)BALF IL-17 concentration in the NAD group were lower than that of the NA group, but were higher than that of the NC group(each P<0.05). Conclusions Airway inflammation in the mouse model of NA were improved by dexamethasone via its inhibition on the exspression of Th17 cells.The enhanced function of Th17 cells proliferation not influenced by dexamethasone,may be responsible for the persistence of the inflammation.
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