Effects Of Three - Step Sequential Method On TGF - β / Smad Signaling Pathway In Rats With Hormone - Dependent Asthma And In Patients With Airway Remodeling During Hormone Withdrawal

Research purpose:The three stage sequential thrapy is put forword as a dynamical treatment option,based on the laws of the pathogenesis changes on the process of withdrawing the steroid in clinical treating the steroid dependent asthma(SDA)patients.Airway remodeling is a very important reason of SDA happening.TGF-β1/Smad is one important signal pathway of all that involved into airway remodeling.the study on the SDA patients and airway remodeling rat model in the process of withdrawing the steroid intends to see the influence and changes of the three stage sequential thrapy to TGF-β1/Smad signal pathway,find out the the correlation with the airway remodeling,implore the regulative effect to the pathway and clarify the mechanism of restraining the airway remodeling.Research method:the research,based on the previous work,will conduct from clinical observation and animal experiment.In the clinical observation patients are randomly devided into 2 groups,one group interfered with the three stage sequential thrapy named treating group,the other with the pulmicort turbuhale named controlling group. Getting to know the changes of TGF-β1/Smad signal pathway between pretherapy and post-treatment by comparing relevant targets in induced sputum,serum and lung function.In animal experiment the rat model is made from simulating clinical patients’ withdrawing steroid process combined with asthma airway remodeling rat model.The rats are randomly devided into 5 groups,airway remodeling group,withdrawing dexamethasone,pulmicort respules,three stage sequential thrapy and normal control group.Finding out the changes of the pathway and the correlation with the airway remodeling by comparing the concentration,positive cell and mRNA expressing of relevant targets in bronchoalveolar lavage fluid and the lung tissue.Result:it is showed that after the intervention the treating group both N%, EOS%,TGF-β1,smad2 in induced sputum and TGF-β1,Smad2,Smad3 in serum decrease obviously,both Smad6 and Smad7 in serum increase obviously,in the meantime the lung function FEV1% and FEV1/FVC% improve obviously compared with that in pretherapy,which has the same effect with pulmicort respules.TGF-β1 has positive relevance with Smad2,Smad3 and has negative relevance with Smad6,Smad7.It is showed that the three stage sequential thrapy can improve the lung function in SDA patients treatment,which is likely to relate to its reducing TGF-β1,Smad2,Smad3 and increasing Smad6,Smad7 in sputum and serum.It is showed in animal experiment that the three stage sequential thrapy can in different extent reduce the concentration of TGF-β1,Smad2,Smad3 and increase that of Smad6,Smad7 in BALF;reduce the positive cell and mRNA expressing of TGF-β1,Smad2,Smad3,Collagen Ⅰ,CollagenⅢ and increase that of Smad6,Smad7 in the lung tissue;reduce the mRNA expressing of TGF-β1,Smad2,Smad3,Collagen Ⅰ(α1),CollagenⅢ and increase that of Smad6,Smad7 in the lung tissue of the airway remodeling rat model of the withdrawing steroid process,which has the same effect with pulmicort respules. It can be noticed that TGF-β1 has positive relevance with Smad2,Smad3,Collagen Ⅰ(α1),CollagenⅢ and has negative relevance with Smad6,Smad7.Conclusion:Comprehensive analyse the results of this two parts,it is showed that the three stage sequential thrapy can improvenot onlythe SDA patients lung function,but also the relevant factors of TGF-β1/Smad signal pathway;the concentration,expressing and mRNA of the relevant factors in the airway remodeling rat model BALF,lung tissue in the process of withdrawing steroid,which is likely to be resulted from regulating the relevant factors TGF-β1,Smad2,Smad3,Smad6,Smad7 of the TGF-β1/Smad signal pathway,correcting imbalance of the regulative and prohibitive proteins in Smads family,restraining the TGF-β1 signal transduction in cell.In this way the deposition content of Collagen Ⅰ,CollagenⅢ in lung tissue gets impoved,which plays the suppressive role in the airway remodeling.