| Objective:To analyze the feasibility of Idiopathic pulmonary fibrosis(IPF)treatment based on the method of Yi-Qi and Blood circulation,and to observe the clinical efficacy of combining Piffinilone with Tonic Yang Returning Five Soup in the treatment of Idiopathic pulmonary fibrosis,and to explore the role of TGF-β1/Smad signaling pathway and ACE2-Ang(1-7)-Mas axis in the pathogenesis of IPF through animal experiments.To further investigate the modulation of TGF-β1/Smad signaling pathway and ACE2-Ang(1-7)-Mas axis in the process of pulmonary fibrosis,and explore the specific mechanisms and targets of Tonic Yang Returning Five Soup in the treatment of pulmonary fibrosis.Methods:(1)Clinical study: Before treatment,there was no significant difference in the general condition of patients in the control group compared with the observation group(P > 0.05),which was comparable.After taking the drugs,the TCM clinical symptom scores,three SGRQ scores and mMRC indexes of patients in the observation group were significantly improved compared with those before treatment(P < 0.05 or P< 0.01),and the 6MWT decreased insignificantly compared with that before treatment,with no statistical difference(P> 0.05);in the control group,the TCM clinical symptom scores and6 MWT decreased significantly(P< 0.01),the three SGRQ scores increased(P< 0.05),and the mMRC score increased,but the difference was not significant.After treatment,the TCM clinical symptom scores,6MWT,SGRQ scores,mMRC indexes and overall efficiency of the observation group were better than those of the control group(P< 0.05).During the treatment,the probability of adverse reactions in the patients of the observation group was lower than that of the control group.(2)Animal experiments: Compared with the model group,the pycnidone group and the medium and high dose groups of Tonic Yang Returning Five Soup had significantly improved lung tissue inflammation,alveolar structure and fiber deposition,reduced the content of HYP,IL-6,IL-1β,TNF-α and Ang II,decreased the expression of TGF-β1,Smad3 protein and TGF-β1,Smad3 and α-SMA mRNA in rats.increased the content of ACE2 and Ang(1-7),increased Smad7 protein and mRNA expression of Smad7 and E-cad,and the differences were statistically significant(P< 0.01 or P < 0.05);the improvement of inflammation,alveolar structure and fibrous deposition in lung tissue was not significant in the low-dose group of Tonic Yang Returning Five Soup,which reduced the HYP,IL-1β,TNF-α,Ang II in rats content,decreased the expression of TGF-β1,Smad3 protein and TGF-β1,α-SMA mRNA,increased the content of ACE2,Ang(1-7)and increased the mRNA expression of Smad7 and E-cad,and the differences were statistically significant(P< 0.01 or P< 0.05).However,the effect on the expression of IL-6,Smad3 mRNA,and Smad7 protein was not significant(P> 0.05).RESULTS:(1)Clinical study: The differences in general data such as age,gender,and mean duration of illness between the control group and the observation group were not statistically significant(P > 0.05)and were comparable.After treatment,the total effective rate of the observation group after treatment was 58.82%,and the score of clinical symptoms in Chinese medicine was reduced compared with that of the control group,and the difference was statistically significant(P < 0.05).After treatment,the 6MWT results of patients in both groups had different degrees of decrease,and the 6MWT results of the observation group were statistically significant compared with the control group(P < 0.05).After treatment,the three scores of respiratory symptoms,activity limitation and disease impact in both groups were statistically significant(P < 0.05),and the three scores in the observation group were better than those in the control group.The mMRC score of the observation group was better than that of the control group after treatment,and the difference was statistically significant(P < 0.05).During the treatment,the probability of adverse reactions in the observation group was lower than that in the control group.(2)Animal experiment: After modeling,the pathology of all groups except the blank group showed different degrees of pulmonary fibrotic changes and collagen deposition,which proved the success of modeling.Compared with the model group,the HYP content in the lung tissues of rats in each dose group of Tonic Yang Returning Five Soup was reduced(P<0.01 or P<0.05).Compared with the model group,the middle and high dose groups of Tonic Yang Returning Five Soup reduced the levels of serum IL-6,IL-1β,TNF-α and Ang II,increased the levels of ACE2 and Ang(1-7),inhibited the protein expression of TGF-β1and Smad3 in lung tissue,up-regulated the protein expression of Smad7 in lung tissue,down-regulated the protein expression of TGF-β1,Smad3 and α-SMA mRNA levels and increased the mRNA levels of Smad7 and E-cad in lung tissue,and the differences were statistically significant(P < 0.01).Compared with the model group,the low-dose group of Tonic Yang Returning Five Soup reduced the levels of serum IL-1β and TNF-α and inhibited the protein expression of lung tissue TGF-β1 in rats,and the differences were all statistically significant(P < 0.05);increased the levels of serum ACE2 and Ang(1-7),decreased the level of Ang II,inhibited the protein expression of lung tissue Smad3 and down-regulated the protein expression of lung tissue mRNA levels of TGF-β1 and α-SMA,and increased mRNA levels of Smad7 and E-cad in lung tissues,and the differences were statistically significant(P < 0.01).However,the differences on the expression of IL-6,Smad3 mRNA,and Smad7 protein were not statistically significant(P > 0.05).Compared with the model group,pirfenidone group could decrease the levels of serum IL-1β,TNF-αand Ang II,increase the levels of ACE2 and Ang(1-7),inhibit the protein expression of TGF-β1 and Smad3 in lung tissue,up-regulate the protein expression of Smad7 in lung tissue,down-regulate the mRNA levels of TGF-β1,Smad3 and α-SMA in lung tissue,and increase the mRNA levels of Smad7 and E-cad in lung tissue,the differences were statistically significant(P < 0.01),and decreasing the serum IL-6 levels in rats,the differences were statistically significant(P< 0.05).CONCLUSION: The treatment of IPF patients with qi deficiency and blood stasis with the combination of tonifying Yang Returning Five Soup and pirfenidone can significantly improve the clinical symptoms of patients,delay the decline of 6MWT in IPF patients,slow down the decline of exercise endurance of patients to a certain extent,improve the quality of life of patients,improve the dyspnea of patients,as well as reduce the adverse effects brought by pirfenidone to patients,and the method of benefiting qi and activating blood has a certain effect on IPF patients with qi deficiency and blood stasis.The mechanism of action of Tonic Yang Returning Five Soup in delaying pulmonary fibrosis may be through the regulation of TGF-β1/Smad signaling pathway and ACE2-Ang(1-7)-Mas axis,which regulates the expression of key proteins in the signaling pathway,thus reducing collagen synthesis and inhibiting the progression of pulmonary fibrosis. |
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