| Objective: To observe the clinical efficacy of Jiawei Huangqi Guizhiwuwu Decoction,the representative prescription of Wenyang Tongmai Tonifying blood method,in the treatment of idiopathic pulmonary fibrosis,and conduct animal experiments to study its mechanism of action,so as to provide more ideas for the future research and treatment of pulmonary fibrosis.Methods:Part I: A total of 42 patients with idiopathic pulmonary fibrosis admitted to the Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Shandong University of Traditional Chinese Medicine from October 2021 to October 2022 were randomly divided into control group and experimental group.They were treated with pirfenidone and added Huangqi Guizhi Wuwu Decoction,respectively.Before and after treatment,the patients were given 6-minute walking test(6MWT),lung function(FVC,DLco)and clinical symptoms of traditional Chinese medicine grading and quantitative scoring,and finally concluded,summarized and analyzed to evaluate the therapeutic effect of each treatment group.Part II: 36 male SD rats were randomly divided into blank group,model group,pirfenidone group,low-dose,medium-dose and high-dose Chinese medicine groups,with 6rats in each group.Except blank group,bleomycin tracheal infusion method was used to construct pulmonary fibrosis rat model.After successful modeling,the rats in each group were given the corresponding drug intragastric administration 28 days later,and the lung wet weight and body weight of the rats were weighed to calculate the lung coefficient.The changes of lung histopathology in each group were observed by hematoxylin-eosin(HE)staining and Masson staining.The content of hydroxyproline(HYP)in rat lung tissue was determined by alkaline hydrolysation.Elisa was used to observe the effects of supplemented Huangqi Guizhi Wuwu Decoction on the contents of TNF-α,IL-6 and IL-1βin serum of rats with pulmonary fibrosis.m RNA expression levels of Nrf2,GPX4,SLC7A11,COX2 and FSP1 in lung tissues were determined by RT-PCR.The contents of GSH,SOD,MDA and Fe ions in rat lung tissue were detected by corresponding kit.Finally,the results were analyzed by SPSS statistical software,so as to explore the mechanism of the treatment of idiopathic pulmonary fibrosis by added Huangqi Guizhi Wuwu Decoction.Results:Part I: Clinical study results showed that adding Huangqi Guizhiwuwu Tang group could prolong the 6MWT distance of IPF patients,and the difference before and after treatment was statistically significant(P<0.05),while the 6MWT of pirfenidone group before and after treatment showed a trend of decrease,and the difference was not statistically significant(P>0.05).After treatment,the 6MWT result of Huangqi Guizhi Wuwu decoction group was better than pirfenidone group;For forced vital capacity(FVC)and carbon monoxide dispersion(DLco),there was no significant difference between the two groups before and after treatment(P>0.05).The added Huangqi Guizhiwuwu decoction group could reduce the total scores of TCM clinical symptoms and improve the clinical symptoms of patients,and the difference was statistically significant before and after treatment(P<0.01),while the total scores of TCM clinical symptoms of the control group did not decrease significantly before and after treatment,and the difference was not statistically significant(P>0.05).The added Huangqi Guizhiwuwu decoction group was better than pirfenidone group.In terms of the incidence of adverse reactions,a total of 4patients in the pirfenidone group had adverse reactions,and 1 patient in the added Huangqi Guizhi Wuwu Tang group had adverse reactions.The incidence of adverse reactions in the added Huangqi Guizhi Wuwu Tang group was lower than that in the control group.Part II: Animal experimental study results showed that compared with blank group,HYP content in other groups was increased,HE staining and Masson three-color staining showed different degrees of inflammatory cell infiltration,pulmonary fibrosis changes and collagen deposition,which proved successful modeling.Compared with model group,serum IL-6,IL-1β and TNF-α contents in pirfenidone group and low-dose,medium-dose and high-dose Chinese medicine groups were decreased,and the differences were statistically significant(P < 0.01).Compared with pirfenidone group,serum IL-1βexpression in high-dose Chinese medicine group was not significantly different(P>0.05).Adding Huangqi Guizhi Wuwu Decoction could increase the expression levels of SOD and GSH in lung tissue and decrease the expression levels of MDA in lung tissue in a dose-dependent manner.Compared with model group,the difference was statistically significant(P<0.01 or P<0.05).Compared with model group,adding Huangqi Guizhi Wuwu Decoction could increase the m RNA expression levels of Nrf2,GPX4 and SLC7A11 in lung tissue,decrease the m RNA expression levels of COX2 and FSP1 and the content of Fe+,and reduce the degree of pulmonary fibrosis in rats,the difference was statistically significant(P<0.01 or P<0.05).Conclusion: The addition of Huangqi Guizhiwuwu Decoction can significantly reduce the clinical symptoms of TCM in patients with idiopathic pulmonary fibrosis,improve the grading and quantitative score of TCM clinical symptoms after treatment,prolong the six-minute walking test distance,and slow down the progress of pulmonary function indicators.The mechanism may be to reduce iron deposition and lipid peroxide accumulation in fibrotic lung tissue by inhibiting oxidative stress and ferroptosis.Therefore,Huangqi Guizhi Wuwu Decoction,the representative prescription of Wenyang Tongmai and blood tonifying method,has high application value in the clinical treatment of IPF. |
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