College of Traditional Chinese Medicine, Changchun University of Chinese Medical, No.1035, Boshuo Road, Jingyue District, Changchun 130017, China.
Department of Pediatrics, The Affiliated Hospital to Changchun University of Chinese Medicine, No. 1478, Gongnong Road, Chaoyang District, Changchun 130021, Jilin, China.
J Pharm Pharmacol. 2024 Aug 2;76(8):1028-1037. doi: 10.1093/jpp/rgae064.
We aim to investigate the effect of YiQi GuBen formula (YQGB) on airway inflammation and airway remodeling in the ovalbumin (OVA)-induced asthma model to further explore the potential mechanisms of YQGB in treating allergic asthma.
Mice were divided into five groups randomly (n = 10): the control group, OVA group, OVA + Dex (0.1 mg/kg) group, OVA + low-dose (1.1 g/kg) YQGB group, and OVA + high-dose (2.2 g/kg) YQGB group. Inflammatory cell count and IgE were detected in bronchoalveolar lavage fluid (BALF). Lung tissue histopathology was observed by using H&E, PAS, Masson, and immunohistochemistry staining. qRT-PCR and western blot were applied to analyze key genes and proteins associated with TLR4 and NF-κB signaling pathways.
In OVA-induced asthma mice, YQGB decreased eosinophils and IgE in BALF. YQGB alleviated the OVA-induced inflammatory infiltration and declined IL-4, IL-5, IL-13, Eotaxin, ECP, GM-CSF, LTC4, and LTD4. YQGB attenuated the OVA-induced goblet cell metaplasia and mucus hypersecretion. YQGB mitigated the OVA-induced subepithelial fibrosis and lowered TGF-β1, E-Cadherin, Vimentin, and Fibronectin. YQGB ameliorated the OVA-induced airway smooth muscle thickening and lessened α-SMA and PDGF levels. YQGB reduced the expression of TLR4, MyD88, TRAF6, IκBα, and p65 mRNAs, and IκBα and p-p65 protein levels were also reduced.
YQGB exhibits the anti-asthma effect by reducing airway inflammation and airway remodeling through suppressing TLR4/NF-κB signaling pathway, and is worth promoting clinically.
本研究旨在探讨益气温本方(YQGB)对卵清蛋白(OVA)诱导的哮喘模型气道炎症和气道重塑的影响,进一步探讨 YQGB 治疗变应性哮喘的潜在机制。
将小鼠随机分为五组(n = 10):对照组、OVA 组、OVA+地塞米松(0.1mg/kg)组、OVA+低剂量(1.1g/kg)YQGB 组、OVA+高剂量(2.2g/kg)YQGB 组。检测支气管肺泡灌洗液(BALF)中炎症细胞计数和 IgE。采用 H&E、PAS、Masson 和免疫组化染色观察肺组织病理变化。qRT-PCR 和 Western blot 用于分析与 TLR4 和 NF-κB 信号通路相关的关键基因和蛋白。
在 OVA 诱导的哮喘小鼠中,YQGB 降低了 BALF 中的嗜酸性粒细胞和 IgE。YQGB 减轻了 OVA 引起的炎症浸润,降低了 IL-4、IL-5、IL-13、Eotaxin、ECP、GM-CSF、LTC4 和 LTD4。YQGB 减轻了 OVA 诱导的杯状细胞化生和粘液高分泌。YQGB 减轻了 OVA 引起的黏膜下纤维化,降低了 TGF-β1、E-钙粘蛋白、波形蛋白和纤维连接蛋白。YQGB 改善了 OVA 引起的气道平滑肌增厚,降低了α-SMA 和 PDGF 水平。YQGB 降低了 TLR4、MyD88、TRAF6、IκBα 和 p65 mRNA 的表达,以及 IκBα 和 p-p65 蛋白水平。
YQGB 通过抑制 TLR4/NF-κB 信号通路,减轻气道炎症和气道重塑,发挥抗哮喘作用,具有临床推广价值。