Dynamic Changes Of TGF-β1/Smads Pathway In Airway Remodeling In Asthma Rats Model And Chai-pu-tang's Effection

Objective:The purpose of this study was to explore dynamic changes of TGF -β1/Smads pathway in airway remodeling in asthma rats model, understanding its role in asthma pathogenesis mechanism.At the same time,to study the possible mechanism which chai-pu-tang cures bronchial asthma.Method:Seventy healthy adult male rats were randomly divided into group A of 10 ,group B of 60(group B1 of 10 is two-week asthmatic group , group B2 of 10 is four-week asthmatic group , group B3 of 10 is eight-week asthmatic group, group B4 of 10 is two-week chai-pu-tang group, group B5 of 10 is four-week chai-pu-tang grou -p, group B6 of 10 is eight-week chai-pu-tang group) ; to copy asthma model with ato -mization ovalbumin , to execute asthma rats after exciting asthma 2 weeks, 4 weeks and 8 weeks , using reverse transcription polymerase chain reaction (RT-PCR) to dete -ct expression level of TGF-β1 andα-SMA mRNA,and using Immunohistochemical staining to detect protein expression of TGF-β1,α-SMA, Smad3, Smad4 and Smad7 in airway, using image analysis method to measure rat airway morphological parame -ters.Results:1. The changes in airway remodeling of asthmatic rats: Stimulated rats after 2 weeks of asthma began to appear a large number of inflammatory cell infiltrati -on around the bronchial wall , airway smooth muscle thickening, goblet cell hyperpla -sia with mucus hypersecretion, excessive collagen deposition, basement membrane thickening; The airway smooth muscle and airway wall is thicker in four-week asthm atic group than two–week asthmatic group, the difference was significant (P <0.05); The airway smooth muscle is clearly thicker and the lumen is more narrow in eight- week asthmatic group compared with than four–week asthmatic group, the difference was significant (P <0.05).2. The protein expression of TGF-β1,α-SMA, Smad3 ,Smad4 and Smad7 and the mRNA expression level of TGF-β1,α-SMA in the airway of asthmatic rats: After stim -ulating asthma two weeks, the protein expression of TGF-β1,α-SMA, Smad3 and Sm -ad4 and the mRNA expression level of TGF-β1,α-SMA increased in bronchial asthma rats airway, but Smad7 protein expression decreased; After stimulating asthma four wee -ks, the protein expression of TGF-β1,α-SMA, Smad3 and Smad4 and the mRNA expr -ession level of TGF-β1,α-SMA significantly increased in bronchial asthma rats airway , but Smad7 protein expression significantly decreased,compared with two-week asthm -atic group, the difference was significant (P<0.05 ). After eight weeks, the protein expr -ession of TGF-β1,α-SMA, Smad3 and Smad4 and the mRNA expression level of TGF -β1,α-SMA significantly increased, but Smad7 protein expression significantly decreased, compared with four–week asthmatic group, the difference was significant(P<0.05).On the other hand, the chai-pu-tang two-week groups compared with two-week asthmatic groups, the protein expression of TGF-β1,α-SMA, Smad3 and Smad4 and the mRNA expression level of TGF-β1,α-SMA significantly decreased, but Smad7 protein expression significa -ntly increased, the difference was significant(P<0.05); the chai-pu-tang four-week groups compared with four-week asthmatic groups, the protein expression of TGF-β1,α-SMA, Smad3 and Smad4 and the mRNA expression level of TGF-β1,α-SMA significantly decre -ased, but Smad7 protein expression significantly increased, the difference was significant (P<0.05); the chai-pu-tang eight-week groups compared with eight-week asthmatic groups, the protein expression of TGF-β1,α-SMA, Smad3 and Smad4 and the mRNA expression level of TGF-β1,α-SMA significantly decreased, but Smad7 protein expression signific -antly increased, the difference was significant(P<0.05);However, the chai-pu-tang groups compared with control group, the protein expression of TGF-β1,α-SMA, Smad3 and Smad4 and the mRNA expression level of TGF-β1,α-SMA increased, but Smad7 protein expression decreased; the difference is significant (P <0.05).Conclusion:1. With stimulated time prolonging, the change of asthmatic air -way remodeling is a dynamic process, the expression ofα-SMA increased gradually, the airway smooth muscle thicken gradually.2. TGF-β1/Smads pathway shows the process of dynamic change in airway remo -deling in asthma rats model. TGF-β1, Smad3 and Smad4 promote airway remodeling, but Smad7 inhibits airway remodeling.3. The mechanism that chai-pu-tang inhibits bronchial asthma airway remodeling is likely correlation with TGF-β1/Smads pathway.