摘要
目的研究Wnt/β-catenin信号通路在哮喘气道炎症和气道重塑中的作用,探讨青蒿琥酯(artesunate,ART)治疗哮喘的可能机制。方法采用卵白蛋白(OVA)激发和雾化吸入的方式建立哮喘模型,并予以药物治疗。观察各组大鼠肺组织的病理形态改变、外周血、支气管肺泡灌洗液(BALF)白细胞计数;Image-Pro plus 6.0图像分析软件测量大鼠肺组织支气管壁厚度和平滑肌厚度;免疫组化法检测大鼠肺组织β-catenin和WISP-1表达情况,RT-PCR检测大鼠肺组织WISP-1表达情况,ELISA法检测血清及BALF中IL-6的表达情况。结果 ART干预哮喘组大鼠气道炎性细胞浸润、支气管壁厚度、平滑肌厚度均明显低于哮喘组大鼠,差异有统计学意义(P<0.01);ART干预哮喘组肺组织β-catenin、WISP-1蛋白和WISP-1 m RNA的表达均明显低于哮喘组,差异有统计学意义(P<0.01);ART干预哮喘组大鼠血清及BALF中IL-6水平表达均明显低于哮喘组,差异有统计学意义(P<0.01)。结论 ART改善哮喘大鼠气道炎症及气道重塑的机制可能与抑制Wnt/β-catenin信号通路活性及下调IL-6水平有关。
Objective To investigate the role of Wnt/β - catenin signaling pathway in airway inflammation and airway remodeling in asthmatic rats, and to explore the possible molecular mechanism of artesunate （ART） in the treatment of asthma. Methods Forty - eight SD rats were randomly divided into normal group, asthmatic group, dexamethasone group, low - dose artesunate group, middle - dose ar- tesunate group and high - dose artesunate group. Asthmatic models were established hy ovalbumin （OVA） challenge and aerosol inhala- tion, and were treated with drugs. The morphological changes of lung tissue, the white blood cell count and the white blood cell count of bronchoalveolar lavage fluid （BALF） were observed in each group. The bronchial wall thickness and smooth muscle thickness were meas- ured by Image - Pro plus image analysis software. The expressions of β- catenin and WISP - 1 in lung tissue were detected by immuno- histochemistry and RT - PCR respectively. The expression of IL - 6 in serum and BALF was detected by ELISA. Results The artesunate group rats, airway inflammatory cells infiltration, the smooth muscle thickness, bronchial wall thickness were significantly lower than those in asthma group, and the difference was statistically significant （P 〈 0.01 ）. The expression of artesunate group β - catenin, WISP - 1 protein and WISP- 1 mRNA were significantly lower than those in asthma group, and the difference was statistically significant （P 〈 0. 01 ）. The level of IL - 6 in serum and BALF of artesunate group was significantly lower than that of asthmatic group （ P 〈 0.01 ）. Conclusion The possible mechanism of artesunate to improve airway inflammation and airway remodeling in asthmatic rats related to the inhibition of Wnt/ beta - catenin signaling pathway activity and down - regulation of IL - 6 levels.
作者
姚孝昆
万玉峰
郑玉龙
Yao Xiaokun Wan Yufeng Zheng Yulong(Xuzhou Medical University, Jiangsu 221004, China)
出处
《医学研究杂志》
2017年第9期151-156,共6页
Journal of Medical Research
