| Objective: To observe the clinical effect of Jiawei Buyang Huanwu Decoction in the treatment of idiopathic pulmonary fibrosis,conduct animal experiments,explore its mechanism of action,hoping to provide more methods for the treatment of this disease in the future.Methods: Part 1: Analyzing 34 patients with idiopathic pulmonary fibrosis admitted from September 2019 to September 2020 in the Outpatient Department of Pulmonary Diseases of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine,patients are divided into two groups,respectively,using Jiawei Buyang Huanwu Decoction Treat with pirfenidone,and performing TCM clinical symptom classification quantification score and six-minute walk test(6MWT)before and 3 months after the treatment,thus observing its effect.The second part: 36 male SD rats were randomly divided into blank group,model group,pirfenidone group,and low,medium and high dose groups of Jiawei Buyang Huanwu Decoction,with 6 rats in each group.Except for the blank group,all rats were replicated with the bleomycin tracheal instillation method,thus replicating the rat pulmonary fibrosis model,and the corresponding drug intervention was given after the successful model building.The rats were sacrificed 28 days after the administration.The effects of Jiawei Buyang Huanwu Decoction on lung histopathology was observed by hematoxylin-eosin(HE)staining and Masson’s trichrome staining;the effects of Jiawei Buyang Huanwu Decoction on VEGF,PDGF-BB and TGF-β1 levels in serum of rats with pulmonary fibrosis was observed by ELISA;Western Blotting and PCR methods were adopted to detect the expression of Wnt/β-catenin and TGF-β1/Smad3 signaling pathway related signal proteins and corresponding m RNA in lung tissue;the immunohistochemical staining method was used to observe the expression levels ofα-SMA,COL1A1,E-cad and v WF,which are related to the epithelial-mesenchymal transition(EMT)indicators in lung tissues.Therefore,the treatment of idiopathic diseases with Jiawei Buyang Huanwu Decoction Possible mechanism of pulmonary fibrosis was detected.Results: Part 1: Before treatment,no significant differences existed in the two groups of patients in gender,age,course of disease,TCM clinical symptom classification and quantitative scores,and 6MWT(P>0.05),and they were comparable.The 6MWT of the Jiawei Buyanghuanwu Decoction group showed a downward trend before and after treatment,and no significant difference was reflected(P>0.05).All clinical symptoms of traditional Chinese medicine were improved,except for chest pain.Significant differences were observed there(P<0.05);the 6MWT of the pirfenidone group showed a downward trend before and after treatment,and there was a significant difference(P<0.05).There were no significant differences in the clinical symptoms of TCM except for cough(P>0.05).A significant difference was observed in the total score of TCM clinical symptom scores and symptom efficacy between the Jiawei Buyang Huanwu Decoction group and the pirfenidone group after treatment,and the Jiawei Buyang Huanwu Decoction group performs better than the pirfenidone group,which is statistically significant(P<0.05).The second part: After the modeling,except for the blank group,the HE staining and Masson’s trichrome staining in other groups showed pulmonary fibrosis and collagen deposition of varying degrees,proving the success of the modeling.Jiawei Buyang Huanwu Decoction reduces the degree of pulmonary fibrosis in rats,as well as the levels of VEGF,PDGF,and TGF-β1 in serum,and down-regulates Wnt3 a,β-catenin,GSK-3β,Smad3,α-SMA,COL1A1,v WF in lung tissue.The expression level of E-cad was up-regulated,and inhibited Wnt3 a m RNA,β-catenin m RNA,GSK-3β m RNA,and Smad3 m RNA levels in a dose-dependent manner,which was significantly different from the model group(P<0.05);compared with the model group,pirfenidone improved the degree of pulmonary fibrosis in rats,reduced the level of TGF-β1 in serum,and down-regulated GSK-3β,Smad3,Wnt3 a,GSK-3β m RNA,Smad3 m RNA,COL1A1,the expression levels of α-SMA and v WF and the up-regulation of E-cad expression levels were significantly different(P<0.05).However,no significant effect showed up on the expressions of PDGF-BB,β-catenin,β-catenin m RNA,and Wnt3 a m RNA(P>0.05).Moreover,the efficacy is lower than that of the Jiawei Buyang Huanwu Decoction group.Conclusion: Jiawei Buyang Huanwu Decoction can significantly improve the TCM clinical symptom classification and quantitative score and 6MWT experimental results of patients with idiopathic pulmonary fibrosis.The mechanism may be through the down-regulation of Wnt/β-catenin and TGF-β1/Smad3 signaling pathways.It is realized by the expression of key signal transduction proteins,inhibition of EMT process and abnormal angiogenesis in fibrotic lung tissue. |
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