Abstract
BackgroundAsthma is characterized by chronic airway inflammation, leading to structura1 changes in the airway, collectively termed airway remodeling. Airway remodeling is thought to contribute to airway hyper responsiveness and irreversible airflow limitation. The combination of Herba Epimedii (HE) and Fructus Ligustri Lucidi (FLL) decoction and the systemic administration of glucocorticoids (GC) had a synergistic inhibitory action on airway inflammation in the asthmatic model rats. However, the effects of the combination on airway remodeling have not been studied and compared. In the present study, we investigated the effects of the co-administration of combined extracts of HE and FLL with inhaled GC (budesonide) on airway remodeling in the rat asthmatic model induced by ovalbumin (OVA).MethodsMale Sprague-Dawley rats were sensitized to intraperitoneal OVA followed by repetitive OVA challenge for 7 weeks. Treatments included extracts of HE and FLL (Extracts for short, 100 mg/kg by gastric perfusion), budesonide (1 mg budesonide suspension in 50 ml sterile physiological saline, 3 rats in an ultrasonic nebulizer by nebulized inhabation with a flow of 1.6 ml/min for 30 min), and co-administration of extracts of HE and FLL with budesonide (Co-administration for short) for 4 weeks. Lung histomorphometry and bronchoalveolar lavage fluid (BALF) cell count were assessed 24 h after the final OVA challenge. Levels of interleukin (IL)-4, IL-5 and IgE were measured by ELISA. Expressions of Collagen I and Collagen III were tested by immunohistology. Expressions of transforming growth factor (TGF) -β1, TGF-β2 and Smads mRNA were measured by quantitative real-time PCR.ResultsExtracts, budesonide and Co-administration significantly reduced allergen-induced increases in the serum levels of IL-4, IL-5 and IgE, the number of eosinophils in BALF, goblet cell hyperplasia, Collagen III integral optical density (IOD) and the mRNA expression of TGF-β2 and Smad2. Extracts and Co-administration could depress the IOD level of Collagen I and the positive area of Collagen I and Collagen III. Budesonide and Co-administration significantly alleviated the thickening of airway wall. Only Co-administration significantly decreased collagen deposition according to the morphometry of Masson’s-stained lung sections, the thickening of airway smooth muscle layer, the number of lymphocytes in BALF and the mRNA expression of TGF-β1 and Smad3, and this was associated with a significant increase in levels of Smad7 mRNA.ConclusionsThe findings suggested that the combination of budesonide and the herbal extracts had a better synergistic effect on airway remodeling in OVA-reduced asthma rats than the single use of budesonide.
Highlights
asthma model group (Asthma) is characterized by chronic airway inflammation, leading to structura1 changes in the airway, collectively termed airway remodeling
Effects of budesonide and the herbal extracts on airway remodeling in hematoxylin and eosin (H&E) sections To determine whether budesonide and the herbal extracts were involved in the development of airway remodeling, we evaluated the peribronchial cellular infiltration and airway smooth muscle thickness in all experimental rats
For Area of smooth muscle (Wam)/perimeter of basement membrane (Pbm) (Fig. 1c), the asthma model group had an increased smooth muscle layer compared with the normal control group (P < 0.01), and only the Co-administration group could reduce myocyte hyperplasia (P < 0.05)
Summary
Asthma is characterized by chronic airway inflammation, leading to structura changes in the airway, collectively termed airway remodeling. We investigated the effects of the co-administration of combined extracts of HE and FLL with inhaled GC (budesonide) on airway remodeling in the rat asthmatic model induced by ovalbumin (OVA). When moderate or high doses are required to control symptoms, adverse effects such as growth stunting in children [12], suppression of the hypothalamic-pituitary-adrenal (HPA) axis [13, 14], and osteopenia [15] may be observed. For these reasons, effective therapies that are targeted at severe asthma and that can inhibit asthma airway remodeling are needed
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