| Objective:To explore the clinical effect of Jiaweibuyanghuanwu decoction in the treatment of pulmonary fibrosis,and to explore the specific mechanism and target of Jiaweibuyanghuanwu decoction in the treatment of pulmonary fibrosis from the point of view of cell level and signal pathway,in order to provide new ideas for the treatment of pulmonary fibrosis.Methods:1.Clinical study: 32 patients with IPF were randomly divided into two groups,with pirfenidone as the control group and Jiaweibuyanghuanwu decoction as the observation group.The treatment cycle was 12 weeks.The dyspnea score,fingertip oxygen saturation,FVC and DLco in lung function,St.George respiratory questionnaire score of the two groups before and after treatment were compared to explore the clinical therapeutic effect of Jiaweibuyanghuanwu decoction on pulmonary fibrosis.2.Cell experiment: PMVECs was induced by TGF-β 1.PMVECs was randomly divided into 8 groups: group 1(blank group),group 2(model group),group 3(blank serum group),group 4(Drug-containing serum of Buyanghuanwu decoction group),group 5(low concentration Drug-containing serum of Jiaweibuyanghuanwu decoction group),group6(medium concentration Drug-containing serum of Jiaweibuyanghuanwu decoction group),group 7(high concentration Drug-containing serum of Jiaweibuyanghuanwu decoction group),group 8(Drug-containing serum of pirfenidone group).The ability of cell migration was detected by Transwell,lumen formation was detected by Tube Formation method,p-ERK1/2 protein expression was detected by Western Blot,VEGF、IL-6was detected by Elisa,ERK1/2mRNA,MEK1/2mRNA,CREBmRNA and VEGFR2 mRNA were detected by PCR.Results:1.Clinical study: there was no significant difference in baseline data and observation indexes between the two groups before treatment,such as age,sex,course of disease and so on.After treatment,the dyspnea score and St.George’s respiratory questionnaire score of patients in Jiaweibuyanghuanwu decoction group were improved,but the objective indexes such as Sp O2,DLco and FVC had no significant change.During the treatment,there were no obvious adverse reactions and side effects.The total effective rate is 87.5%.Compared with before treatment,dyspnea score,Sp O2,DLco and FVC were not significantly improved in pirfenidone group,but St.George respiratory questionnaire score was higher than that before treatment,indicating that the quality of life of the patients decreased.One patient developed solar dermatitis during treatment.The effective rate of treatment was 62.5%.2.Cell experiment:(1)the level of MEK1/2mRNA,ERK1/2mRNA and p-ERK1/2in PMVECs,MAPK/ERK1/2 pathway was increased induced by TGF-β 1,which indicated that MAPK/ERK1/2 signal pathway was activated.(2)TGF-β 1induced the cells migration and tubule formation of PMVECs,and the expression of pro-angiogenic factors VEGF,VEGFR2 mRNA,CREBmRNA and IL-6 increased,indicating that the angiogenesis model of PMVECs has been established.(3)the drug-containing serum of Buyanghuanwu decoction,Jiaweibuyanghuanwu decoction and pirfenidone all inhibited MAPK/ERK1/2 pathway,decreased the expression of pro-angiogenic factors VEGF,VEGFR2 mRNA,CREBmRNA and IL-6,and inhibited cell migration and tubule formation.(4)the concentration composition of drug-containing serum of Jiaweibuyanghuanwu decoction had a certain dose-effect trend,and the effect of high concentration group was better than that of low and medium concentration groups.(5)the effect of high concentration group of Jiaweibuyanghuanwu decoction drug-containing serum on inhibiting MAPK/ERK1/2 pathway,reducing the expression of pro-angiogenic factors,inhibiting cell migration and tubule formation was better than that of Buyanghuanwu decoction drug-containing serum group;(6)the effects of each concentration group of Jiaweibuyanghuanwu decoction drug-containing serum were different from those of pirfenidone drug-containing serum group.Conclusion:The clinical efficacy of Jiaweibuyanghuanwu decoction in the treatment of IPF is better than that of pirfenidone.It can alleviate the symptoms of dyspnea and improve the quality of life of the patients.It is safe to use the medicine,and there are no obvious adverse reactions and side effects,but there is no obvious improvement on the objective indexes such as Sp O2,FVC,DLco and so on.The cell experiment showed that the drug-containing serum of Jiaweibuyanghuanwu decoction could reduce the expression of pro-angiogenic factors such as VEGF,VEGFR2 mRNA,CREBmRNA and IL-6,and reduce the transcription level of MAPK/ERK1/2 pathway marker protein ERK1/2mRNA,MEK1/2mRNA and the level of ERK1/2 phosphorylation.It is speculated that the drug-containing serum of Jiaweibuyanghuanwu decoction may down-regulate the levels of pro-angiogenic factors VEGF,VEGFR2 mRNA,CREBmRNA and IL-6 by inhibiting MAPK/ERK1/2 signal pathway.Reduce angiogenesis and remodeling,thereby delaying the process of pulmonary fibrosis. |
