Step Sequential Therapy On Steroid-dependent Asthma TGF-β1 / Smad Signaling Pathway In The Regulation Of The Patient

Glucocorticoids play an important role in the treatment of bronchial asthma by relieving airway inflammation.A small number of patients is not sensitive to hormone treatment,they have to apply long-term or large quantity use of glucocorticoids. Once reduce the dosage of oral steroids asthma will recur or to be more serious,knowm as Steroid-dependent asthma (SDA).Modern studies suggest that TGF-β1is one of the important cellular molecules in the pathogenesis of asthma which is provided with function of inducing inflammation and aggravating airway remodeling. Smad help TGF-β1to complete signal tran-smission as it’s following signaling molecules. Which Smad2and Smad3promote TGF-β1signal transduction whlie Smad6and Smad7have inhibition of TGF-β1signal transduction.Previous studies indicate that changes in the pathogenesis of SDA is refle cted in three aspects. At the first, the body usually presents in the form of deficiency of Yin and hyperactivity of evil fire after use the glu-cocortic oid as the leading treatment medication. Then, Yin and Yang are increasingly frail in pace of reduction in the amount of steroid. Finally, deficiency of kidney-yang becomes the most prominent manifestations during steroid has been disable ed. The three-stage sequential therapy could reduce the oral steroid dose, decrese the inhaling frequency of Vantolin,promote the recovery of lung function and improve the quality of life of SDA patients.Objective:To explain the changing rules of TGF-β1/Smad signal transduc tion pathway with SDA during steroid withdrawal before and after. To indicate the therapeutic efficacy of three-step sequential therapy in TGF-β1/Smad signal transduction pathway.Method:The patients in the trial were devided into two groups which were treatment group(n=15)and control group (n=16).The treatment group was treated by the three-step sequential therapy while the control group was treated by inhaling steroid (Budesonide and Formoterol Fumarate Powder for Inhalation) with dose of160μg/4.5μg, every two suction twice daily inhalation. The period of treatment was12weeks. To detect the concentration of proportion of neutrophils and eosinophils in SDA patients’sputum,TGF-μ1, Smad2、Smad3、Smad6、Smad7in serum and induced sputum by Enzyme-Linked ImmunoSorbent Assay(ELISA), and forced expiratory volume in one second(FEV1)、FEV1/FVC (forced vital capacity) before and after the treatment.Results:1. After the treatment, the concentration of TGF-β1, Smad2、Smad3in serum of the two groups were both decreased (P<0.01); While the concentration of Smad6、 Smad7in serum of the two groups were increased (P<0.01). The concentration of TGF-β1, Smad2in induced sputum of the two groups were both decreased (P<0.01) after the treatment. Smad3、Smad6、Smad7of induced sputum were negative on the two groups of patients before and after the treatment.2. The percentage of eosinophils and neutrophils of sputum were both decreased (P<0.05, P<0.01) of two groups after treatment, there are positive correlation exist between the TGF-β1and the percentage of eosinophils in sputum of the two groups before and after the treatment (P<0.05)3. After the treatment,FEV1%, FEV1/FVC of the two groups were both degraded significantly(P<0.05).The positive correlation exist between the TGF-β1and FEV1%、FEV1/FVC in both serum and induced sputum of the two groups before and after the treatment.Concilsion:Three-step sequential therapy achieve to reduce airway infla mmation and restrain airway remodeling by reducing the secretion of TGF-β1, reducing Smad2, Smad3concentration, improve Smad6, Smad7content, regulating and controlling the balance of TGF-β1/Smad signal transduction pathways.