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[糖皮质激素对哮喘气道黏液分泌的影响:哮喘小鼠模型实验]

[Effects of glucocorticoid on airway mucus secretion in asthma: experiment with asthmatic mouse model].

作者信息

Liu Jian-bo, Zhang Zhen-xiang, Xu Yong-jian, Xing Li-hua, Zhang Hui-lan

机构信息

Department of Respiratory Disease, Second Affiliated Hospital, Zhengzhou University, Zhengzhou, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2006 Sep 19;86(35):2491-4.

Abstract

OBJECTIVE

To study the effects of glucocorticoid on airway mucus secretion in asthma.

METHODS

Twenty-four BALB/c mice were randomly divided into 3 equal groups: asthma group [ovalbumin (OVA) and aluminum hydroxide were injected intraperitoneally on day 0 and day 14 so as to establish mouse asthma model and aerosol inhalation of OVA PBS was conducted for 30 min on the days 21, 22, and 24], asthma + dexamethasone group (OVA and aluminum hydroxide were injected intraperitoneally on days 0 and 14, aerosol inhalation of OVA PBS was conducted for 30 min on the days 21, 22, and 24, and dexamethasone was injected intraperitoneally 1 hour before the aerosol inhalation), and control group (aerosol inhalation of PBS was conducted instead). Twenty-fours hours after the last exposure the mice were anesthetized deeply and their left lungs were excised to collect the bronchoalveolar lavage fluid (BALF) to calculate the numbers of total cells and eosinophils, then Alcian blue/periodic acid-Schiff staining and immunohistochemistry of the air passage were conducted to measure the expression levels of MUC5AC mRNA and protein and interleukin-4 (IL-4) mRNA.

RESULTS

The numbers of total cells in the BALF of the asthma group were (12.50 +/- 0.14) x 10(9)/L and (1.12 +/- 0.10) x 10(9)/L respectively, both significantly higher than those of the control group, (6.49 +/- 0.05) x 10(9)/L and (0.05 +/- 0.02) x 10(9)/L respectively (both P < 0.01), and were significantly higher than those of the asthma + dexamethasone group, (6.68 +/- 0.03) x 10(9)/L and (0.06 +/- 0.01) x 10(9)/L respectively too (both P < 0.01). The levels of MUC5AC mRNA, MUC5AC protein, and IL-4 mRNA of the asthma group were 0.5341 +/- 0.303, 0.1906 +/- 0.0008, and 0.6265 +/- 0.0932 respectively, all significantly higher than those of the control group (0.1994 +/- 0.0128, 0.1194 +/- 0.0007, and 0.2389 +/- 0.0289 respectively, all P < 0.01), and those of the asthma + dexamethasone group (0.2729 +/- 0.0345, 0.1456 +/- 0.0003, and 0.2424 +/- 0.0260, all P < 0.05). The MUC5AC protein expression and mRNA expression, and IL-4 mRNA expression of the asthma group were 0.1906 +/- 0.0008, 0.5341 +/- 0.0303, and 0.6265 +/- 0.0932 respectively, all significantly higher than those of the control group (0.1194 +/- 0.0007, 0.1994 +/- 0.0128, and 0.2398 +/- 0.0289 respectively, all P < 0.01). The MUC5AC protein expression and mRNA expression, and IL-4 mRNA expression of the asthma + dexamethasone group were 0.1456 +/- 0.0003, 0.2729 +/- 0.0345, and 0.2424 +/- 0.0260 respectively, all significantly lower than those of the asthma group (all P < 0.01). The MUC5AC protein expression and mRNA expression of the asthma + dexamethasone group were still significantly higher than those of the control group (both P < 0.01), however, the IL-4 mRNA expression of the asthma + dexamethasone group was not significantly different from that of the control group (P > 0.05).

CONCLUSION

Relieving the inflammation, glucocorticoid may play a role in the treatment of excessive mucus production through down-regulating the expression of MUC5AC and of IL-4.

摘要

目的

研究糖皮质激素对哮喘气道黏液分泌的影响。

方法

将24只BALB/c小鼠随机分为3组,每组8只:哮喘组(于第0天和第14天腹腔注射卵清蛋白(OVA)和氢氧化铝以建立小鼠哮喘模型,并于第21、22和24天进行OVA PBS雾化吸入30分钟)、哮喘+地塞米松组(于第0天和第14天腹腔注射OVA和氢氧化铝,于第21、22和24天进行OVA PBS雾化吸入30分钟,并在雾化吸入前1小时腹腔注射地塞米松)和对照组(改为雾化吸入PBS)。末次暴露24小时后,将小鼠深度麻醉,切除左肺以收集支气管肺泡灌洗液(BALF),计算总细胞数和嗜酸性粒细胞数,然后进行气道的阿尔辛蓝/过碘酸-希夫染色及免疫组化,以检测MUC5AC mRNA和蛋白以及白细胞介素-4(IL-4)mRNA的表达水平。

结果

哮喘组BALF中的总细胞数分别为(12.50±0.14)×10⁹/L和(1.12±0.10)×10⁹/L,均显著高于对照组的(6.49±0.05)×10⁹/L和(0.05±0.02)×10⁹/L(均P<0.01),也显著高于哮喘+地塞米松组的(6.68±0.03)×10⁹/L和(0.06±0.01)×10⁹/L(均P<0.01)。哮喘组的MUC5AC mRNA、MUC5AC蛋白和IL-4 mRNA水平分别为0.5341±0.303、0.1906±0.0008和0.6265±0.0932,均显著高于对照组的(0.1994±0.0128、0.1194±0.0007和0.2389±0.0289,均P<0.01),以及哮喘+地塞米松组的(0.2729±0.0345、0.1456±0.0003和0.2424±0.0260,均P<0.05)。哮喘组的MUC5AC蛋白表达和mRNA表达以及IL-4 mRNA表达分别为0.1906±0.0008、0.5341±0.0303和0.6265±0.0932,均显著高于对照组的(0.1194±0.0007、0.1994±0.0128和0.2398±0.0289,均P<0.01)。哮喘+地塞米松组的MUC5AC蛋白表达和mRNA表达以及IL-4 mRNA表达分别为0.1456±0.0003、0.2729±0.0345和0.2424±0.0260,均显著低于哮喘组(均P<0.01)。哮喘+地塞米松组的MUC5AC蛋白表达和mRNA表达仍显著高于对照组(均P<0.01),然而,哮喘+地塞米松组的IL-4 mRNA表达与对照组无显著差异(P>0.05)。

结论

糖皮质激素通过减轻炎症,下调MUC5AC和IL-4的表达,可能在治疗黏液过度分泌中发挥作用。

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