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[氯喹对哮喘小鼠气道高反应性的抑制作用]

[Inhibitory effect of chloroquine on airway hyperresponsiveness in asthmatic mice].

作者信息

Sun Xiao-Chun, Hu Xiao-Yan, Wang Li-Jia, Liu En-Mei, Fu Zhou

机构信息

Department of Respiratory Medicine, Children's Hospital Affiliated to Chongqing Medical University, Chongqing 400014, China.E-mail:

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2015 Jan;35(1):12-6.

Abstract

OBJECTIVE

To investigate the effect of chloroquine on airway hyperresponsiveness in asthmatic mice and explore the possible mechanism.

METHODS

Balb/c mouse models of asthma established using OVA received intraperitoneal injections of chloroquine, dexamethasone, or both prior to OVA challenge. Within 24 h after the final challenge, airway hyper- responsiveness (AHR) of the mice was assessed, and the total cell count and the counts of different cell populations in the bronchoalveolar lavage fluid (BALF) were determined under light microscopy. The severity of lung inflammation was evaluated using HE staining, and the concentrations of IL-6 and PGF2α in the BALF were detected by enzyme-linked immunosorbent assay (ELISA).

RESULTS

Chloroquine pretreatment significantly decreased AHR (P<0.001) in the asthmatic mice and reduced the total cell count (P<0.01), eosinophils (P<0.001), neutrophils (P<0.01), and PGF2α levels in the BALF. Chloroquine combined with low-dose dexamethasone significantly lessened inflammations around the bronchioles (P<0.05) and blood vessels (P<0.01) in the lung tissue, and obviously lowered IL-6 (P<0.05) and PGF2α (P<0.001) in the BALF in the asthmatic mice.

CONCLUSION

Chloroquine can inhibit AHR in asthmatic mice and produce better anti-inflammatory effect when combined with dexamethasone for treatment of neutrophilic asthma.

摘要

目的

探讨氯喹对哮喘小鼠气道高反应性的影响并探究其可能机制。

方法

用卵清蛋白(OVA)建立Balb/c小鼠哮喘模型,在OVA激发前腹腔注射氯喹、地塞米松或两者。在末次激发后24小时内,评估小鼠气道高反应性(AHR),并在光学显微镜下测定支气管肺泡灌洗液(BALF)中的总细胞计数及不同细胞群体计数。用苏木精-伊红(HE)染色评估肺部炎症严重程度,通过酶联免疫吸附测定(ELISA)检测BALF中白细胞介素-6(IL-6)和前列腺素F2α(PGF2α)的浓度。

结果

氯喹预处理显著降低哮喘小鼠的AHR(P<0.001),并减少BALF中的总细胞计数(P<0.01)、嗜酸性粒细胞(P<0.001)、中性粒细胞(P<0.01)及PGF2α水平。氯喹联合低剂量地塞米松显著减轻肺组织中小支气管周围(P<0.05)和血管周围(P<0.01)的炎症,并明显降低哮喘小鼠BALF中的IL-6(P<0.05)和PGF2α(P<0.001)。

结论

氯喹可抑制哮喘小鼠的AHR,与地塞米松联合用于治疗嗜中性粒细胞性哮喘时具有更好的抗炎效果。

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