Study On The Therapeutic Effect Of Yiqi Paidu Tongluo Recipe On COPD Rats And The Mechanism Of Regulating NE/MT

Background:Chronic obstructive pulmonary disease is related to a variety of pathogenesis,including inflammatory reaction,protease-antiprotease imbalance,oxidationantioxidant imbalance,immune reaction and so on.Inflammatory reaction is the key link in the pathogenesis of COPD.The imbalance of protease/antiprotease is the main factor causing airway injury and pulmonary damage.The two factors influence each other and promote each other,which is an important reason for the progress of COPD.Based on the traditional theory of COPD and modern medical research,we put forward the hypothesis of "toxin damaging pulmonary collaterals",based on the theoretical research of previous micro zhengjia.Congenital or acquired AAT reduction is an important reason for the decrease of lung tissue's self-protective function.The increase of NE and the reduction of AAT in lung tissue under the stimulation of cigarette smoke,resulting in the imbalance of NE/AAT,is the main mechanism of lung tissue damage,and the smoke also stimulates the secretion of TGF-(31 in the airway epithelium,which inhibits epithelial cell regeneration and affects the airway.An important factor in repair.The three joint effects cause lung tissue damage,and promote each other,cause cascade reaction,produce more inflammatory factors,protease,active oxygen and so on,causing a vicious cycle,leading to the aggravation of the disease.This is consistent with the evolution process of "toxin damaging pulmonary collaterals".In the previous study,we found that this prescription has the effect of inhibiting the inflammatory response of COPD rats.This study continues to further study the COPD pathological changes in the protease-antiprotease imbalance in airway injury,and explore the effect of Yiqi Paidu Tongluo Recipe on the NE/AAT imbalance in COPD rats.The mechanism of the Chinese medicine treatment of COPD can provide experimental evidence for the therapeutic action of multiple links and targets.Objective:With the change of TGF-?1,NE,AAT and NE/AAT as the breakthrough point,the effect and mechanism of Yiqi Paidu Tongluo Recipe in the treatment of COPD rats were explored,and the molecular biological pathological basis was provided for the hypothesis of "toxic damage pulmonary collateral" pathogenesis.Methods:60 Wistar rats were randomly divided into control group,model group,western medicine group,low dose Chinese medicine group,medium dose Chinese medicine group and high dose Chinese medicine group,10 rats in each group.Model group,western medicine group and Chinese medicine groups were all exposed to cigarette smoke exposure combined with LPS injection into the airway to prepare COPD rat model.The control group and the model group were given the normal saline,10mL/kg,and once daily,and the western medicine group was given budesonide inhalation,once a day,the saline was given to the stomach,10mL/kg,once a day,and the medium dose group was administered to the stomach with the concentration of 17.89g/kg in the concentration of Yiqi Paidu Tongluo,the low dose group and the high dose group were given the middle dose group respectively.1/2 and 2 times concentration of Yiqi Paidu Tongluo Decoction were administered once a day.After 12 weeks,lung function tests,blood and lung tissues were taken for index detection in rats.Results:1.The model of COPD rats was established by smoke stimulation+intratracheal infusion of LPS.The general state of the rats in the model group(mental,physical,death,etc.)was worse than that in the blank group.The inflammatory cell infiltration,emphysema,pulmonary function decreased,the serum NE increased,the AAT decreased,NE/AAT increased,and TGFin the lung tissue.The histopathological findings of the elevated COPD expression were related to COPD.2.General status and pathological results:the general condition of the rats in the treatment group was better than that in the model group,and the pulmonary emphysema and the airway and pulmonary vascular remodeling in the rats were less than that in the model group.3.The results of lung function test:compared with the model group,all the Chinese medicine groups could improve the levels of FVC,FEV0.2,FEV0.2/FVC,PEF,FEF25-75%and MMF in COPD rats,all of which were statistically significant,P<0.05.4.The results of inflammatory factors and protease detection:ELISA results showed that compared with the model group,the level of NE decreased,AAT increased,NE/AAT decreased,and the best effect was in high dose group,P<0.05.The results of qPCR showed that the expression of TGF-?1 mRNA in the lung tissue of the Chinese medicine group decreased and P<0.05 compared with the model group.Western blot results showed that Yiqi Paidu Tongluo recipe could effectively reduce the expression of TGF-?1 protein,P<0.05.5.Protease-antiprotease imbalance and TGF-beta 1:the level of NE and NE/AAT in the rat serum was positively correlated with the expression of TGF-?1mRNA and TGF-?1 protein in the lung tissue,and the level of AAT in the rat serum was negatively correlated with the expression of TGF-?1mRNA and TGF-?1 protein.Conclusions:The prescription of Yiqi Paidu Tongluo can directly regulate the level of NE,AAT and NE/AAT.It can also regulate the level of NE,AAT and NE/AAT by interfering with the expression of TGF-?1 mRNA and TGF-?1 protein.It can reduce the decomposition of elastin in lung tissue,protect lung tissue,improve lung function and treat COPD disease from the two aspects of reducing lung tissue injury and strengthening lung tissue protection.Meanwhile,it also verifies the rationality of the pathogenesis hypothesis of "toxin damaging pulmonary collaterals".