Zhakeer Zibierguli, Hadeer Maierbati, Tuerxun Zumulaiti, Tuerxun Kelibiena
Respiratory Function Test Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Pharmacology. 2017;99(3-4):179-187. doi: 10.1159/000450754. Epub 2017 Jan 4.
Asthma is an inflammatory airway disease characterized by increased infiltration of inflammatory cells into the airways and poor respiratory function. Bufalin is one of the biological ingredients obtained from Chansu. Bufalin was found to possess various pharmacological properties including anti-inflammatory activities. However, the effect of bufalin treatment on asthma has not yet been reported. Therefore, this study aimed to investigate the inhibitory effect of bufalin on asthmatic response in a murine model. A mouse asthma model was developed by ovalbumin (OVA) sensitization and challenge in the BALB/c mice. OVA-specific serum IgE and the levels of interleukin (IL)-4, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF) were determined by an enzyme-linked immunosorbent assay. Recruitment of inflammatory cells into BALF or lung tissues, and goblet cell hyperplasia were evaluated by histological staining. The expression levels of inhibitory subunit of nuclear factor-kappa B (NF-κB) alpha (IκBα) and phosphorylated p65 protein were measured by Western blot analyses. The results demonstrated that bufalin (5 and 10 mg/kg) markedly attenuated hyperresponsiveness, and strongly suppressed the OVA-induced increases of total inflammatory cells including macrophages, eosinophils, lymphocytes, and neutrophils in BALF. The levels of IL-4, IL-5, and IL-13 in BALF and OVA-specific IgE in serum were significantly reduced by bufalin. Histological staining of lung tissues showed that bufalin reduced inflammatory cell infiltration and goblet cell hyperplasia. The results of Western blotting indicated that bufalin suppressed the IκBα degradation from NF-κB, and reduced the level of phosphorylated p65 protein in the lung tissues. These data suggest that bufalin can exert its anti-inflammatory effects possibly through the inhibition of the NF-κB activity.
哮喘是一种炎症性气道疾病，其特征是炎症细胞向气道的浸润增加以及呼吸功能不佳。蟾毒灵是从蟾酥中获得的生物成分之一。已发现蟾毒灵具有多种药理特性，包括抗炎活性。然而，蟾毒灵治疗哮喘的效果尚未见报道。因此，本研究旨在探讨蟾毒灵对小鼠模型哮喘反应的抑制作用。通过对BALB/c小鼠进行卵清蛋白（OVA）致敏和激发建立小鼠哮喘模型。采用酶联免疫吸附测定法测定OVA特异性血清IgE以及支气管肺泡灌洗液（BALF）中白细胞介素（IL）-4、IL-5和IL-13的水平。通过组织学染色评估炎症细胞向BALF或肺组织的募集以及杯状细胞增生情况。采用蛋白质印迹分析测定核因子-κB（NF-κB）α抑制亚基（IκBα）和磷酸化p65蛋白的表达水平。结果表明，蟾毒灵（5和10mg/kg）显著减轻了高反应性，并强烈抑制了OVA诱导的BALF中包括巨噬细胞、嗜酸性粒细胞、淋巴细胞和中性粒细胞在内的总炎症细胞增加。蟾毒灵显著降低了BALF中IL-4、IL-5和IL-13的水平以及血清中OVA特异性IgE的水平。肺组织的组织学染色显示，蟾毒灵减少了炎症细胞浸润和杯状细胞增生。蛋白质印迹结果表明，蟾毒灵抑制了NF-κB的IκBα降解，并降低了肺组织中磷酸化p65蛋白的水平。这些数据表明，蟾毒灵可能通过抑制NF-κB活性发挥其抗炎作用。
