Clinical Efficacy Observation And Mechanism Experiment Of Jiaweibuyanghuanwu Decoction In Treating Idiopathic Pulmonary Fibrosis

Objective:To observe the efficacy of Jiaweibuyanghuanwu Decoction in the treatment of IPF.And through the animal experiments,to explore the pharmacodynamic mechanism of Jiaweibuyanghuanwu Decoction in the treatment of idiopathic pulmonary fibrosis based on the PEDF,inflammatory factors and TRAF6/NF-κB signaling pathway related signal proteins.Methods:Part one:IPF patients with syndrome of blood stasis due to qi deficiency,were randomly divided into observation group and control group in pulmonary outpatient and ward of The Affiliated Hospital of Shandong University of TCM.The control group was treated with Buyanghuanwu Decoction on th basis of routine therapy,and the observation group was treated with epimedium herb and common curculigo rhizome in decoction on the basis of the control group.And the two groups were treated continuously for 12 weeks to observe the scores of TCM syndrome,Medical Research Council（MRC）dyspnoea scale and percutaneous arterial oxygen saturation（Sp O₂）of the two groups.The changes of related indexes before and after treatment were monitored,and the clinical efficacy were discussed.Part two:Established PF model rats,the model was interacted with Buyanghuanwu Decoction normal saline,Jiaweibuyanghuanwu Decoction at low,medium and high doses,and healthy rats were set up as blank group.After 28d treatment,the general condition,lung morphology of the rats were observed.Masson dyeing was used to observe lung organization fibrosis degree,and hematoxylin and eosin staining（HE）was used to observe the grade of pulmonary alveolar inflammation.The levels of serum PEDF,IL-6 and TNF-αwere detected by ELISA method examination.The content of TRAF6 and NF-κB P50 in rats lung tissue was detected by Western Blot and immunohistochemistry technique.The transcriptional-level of TRAF6 m RNA,NF-κB P50m RNA and PEDF m RNA in lung tissues were detected by real-time Quantitative PCR.Results:Part one:（1）The scores of TCM syndrome in the two groups decreased after treatment,the difference was statistically significant（P<0.01）,which was significantly higher in the observation group than in the control group（P<0.01）.（2）The score of m MRC in the two groups increased after treatment,which was significantly lower in the observation group than in the control group（P<0.05）.（3）Comparison of Sp O₂:the score in the two groups decreased after treatment,which was higher in the observation group than in the control group（P<0.05）.Part two:（1）General condition observation:The rats in the blank group were strong and fat,in good mental state,not changed significantly.Other groups rats showed wheezing,reduced diet and activity,matte fur.The results were slightly better,but worse than the blank group after treatment.（2）Pathology:The appearance of lung tissues was always red and pink in the blank group,good elasticity,no bleeding spots or nodules,the surface of the lung tissue was hard,markedly less elastic,some bleeding spots and gray nodules in other groups.Compared with the model group,the bilateral lungs were improved in decoction groups.Compared with the blank group,in other groups,the alveolar structure was destroyed,alveolar inflammation were observed,and there were obvious collagen fiber hyperplasia.Compared with the model group,a lesser extent had showed in decoction groups,and it was significant in high dose group.（3）The expressions of PEDF,IL-6 and TNF-α.The contents of IL-6,TNF-αand PEDF in serum in the model&decoction groups were increased compared with those in the blank group.Compared with the model group,the contents of IL-6 and TNF-αin serum of rats were all decreased in the decoction groups,which of PEDF was increased,and it was significant in high dose group.（4）Expressions of TRAF6 and NF-κB P50:WB and immunohistochemistry technique showed,compared with the blank group,the protein expressions of TRAF6 and NF-κB P50 in the model&decoction group were significantly increased.Compared with the model group,the protein expressions of TRAF6 and NF-κB P50 in the decoction group were decreased,and it was significant in high dose group.（5）The transcriptional-level of TRAF6 m RNA,NF-κB P50 m RNA and PEDF m RNA:Compared with the blank group,the transcriptional-level of TRAF6 m RNA,NF-κB P50 m RNA and PEDF m RNA were increased in the model&decoction group.Compared with the model group,in the decoction group,the transcriptional-level of TRAF6 m RNA and NF-κB P50 m RNA were increased,which of PEDF m RNA was increased,and it was significant in high dose group.Conclusion:The addition of Jiaweibuyanghuanwu Decoction or Buyanghuanwu Decoction to the basic treatment of western medicine can improve the clinical symptoms,and delay the decline of activity endurance,among which,efficacy of observation group is better than which of control group.The mechanism may be through the down-regulation of TRAF6/NF-κB signaling pathway,stimulating the transcription of PEDF m RNA and the expression of PEDF,inhibiting inflammation and abnormal angiogenesis in fibrotic lung tissue.