Mechanism Of Danggui Buxue Tang On Experimental Idiopathic Pulmonary Fibrosis Based On The Correlation Between Qi Deficiency,Blood Stasis And Angiogenesis

Objective: To observe the state of Qi deficiency,blood stasis and angiogenesis in experimental IPF rats,and to reveal its possible pathogenesis;Taking Yi Qihuoxue as the method,Danggui buxue tang(DTB)was selected to intervene,and the mechanism of this side’s regulation of angiogenesis under IPF state was explored.Methods: Forty SPF SD male rats were randomly divided into sham operation group,model group,prednison group and DBT group.Bleomycin was instilled into the trachea to replicate the IPF rat model.Gavage was given24 hours after modeling.The sham operation group and model group were given deionized water(1 m L/100 g),the prednison group was given a prednison aqueous solution(0.5 mg/100 g),and the DBT group was given DBT Chinese traditional medicine free decoction aqueous solution(0.81g/kg/d).Monitor changes in body weight and food intake of rats On the 28 th day of intragastric administration,the rats in each group were subjected to Qi deficiency and blood stasis syndrome score,laser speckle imaging of the dorsal ear vein and weight-bearing swimming test,and lung function tests were performed.Rats were killed by decapitation,the whole lungs were taken out of the chest,weighed,and the lung index was calculated;Hematoxylin eosin(He)staining and Szapiel score was used to evaluate the degree of alveolitis,and to measure the changes of the thickness of the pulmonary arterial wall,vascular wall thickness/ vascular external diameter(WT%),vascular wall area/ total vascular area(WA%);Masson staining and Ashcroft score was used to evaluate the degree of pulmonary fibrosis;lung tissue transparency was detected Hyaluronic acid(HA),laminin(LN)and hydroxyproline(HYP)content;immunohistochemical staining to observe hypoxia-inducible factor-1 alpha(HIF-1α),endostatin and CD34 protein expression,measuring microvessel density(MVD);Real time fluorescence quantitative PCR(RT-q PCR)and Western blot(WB)respectively The expressions of HIF-1α,Platelet derived growth factor(PDGF),Pigment epithelium-derived factor(PEDF),endostatin m RNA and protein were detected.Results:1.General condition of ratsFrom the 4th day after the operation,the rats in the sham-operated group had high mobility,smooth and smooth hair,light pink skin on the lips,ears,and tip of the nose,and body weight and food intake increased steadily.Rats in the model group suffered from lack of energy,low mobility,lack of gloss,shortness of breath,wheezing in the larynx,and later the lips,ears,tip of the nose,and nails appeared dark purple.Body weight and food intake decreased significantly after modeling,and began to increase slowly on the 4th day,but significantly lower than the sham operation group(P < 0.01).2.The scores of rats with Qi deficiency and blood stasis in each groupCompared with the sham operation group,the model group’s Qi deficiency and blood stasis syndrome scores were significantly increased,and the weight-bearing swimming time and blood perfusion volume were significantly reduced(P < 0.01).Compared with the model group,the syndrome score of Qi deficiency and blood stasis in the DBT group was significantly reduced,and the weight-bearing swimming time and blood perfusion volume were significantly increased(P < 0.01).Compared with the prednison group,the DBT group had significantly lower syndrome scores for Qi deficiency and blood stasis,and the weight-bearing swimming time and blood perfusion volume were significantly increased(P < 0.05 or P < 0.01).3.Rat lung function,lung index,lung tissue HA,LN,HYP content,Szapiel score,Ashcroft score,the thickness of the pulmonary arterial wall,WT%,WA%,MVD detectionCompared with the sham operation group,lung function respiratory resistance(Rrs),elastance(Ers),Newtonian airway resistance(Rn),tissue elastance(H)increased,lung function compliance(Crs),tissue damping(G)decreased(P < 0.01);lung index,lung tissue HA,LN,HYP content,Szapiel score,Ashcroft score,the thickness of the pulmonary arterial wall,WT%,WA%and MVD were significantly increased(P < 0.05 or P < 0.01);compared with the model group,the lung function Rrs,Ers,Rn,H in the DBT group decreased,and the lung function Crs and G increased(P < 0.01);Lung index,lung tissue HA,LN,HYP content,Szapiel score,Ashcroft score,the thickness of the pulmonary arterial wall,WT%,WA% and MVD were significantly reduced(P < 0.05 or P <0.01).4.Expression characteristics of HIF-1α,PDGF,PEDF,endostatin and CD34Compared with the sham operation group,the mean optical density(MOD)of lung tissue HIF-1α,endostatin and CD34 in the model group was significantly increased(P < 0.01);m RNA and protein expression levels of HIF-1α,PDGF,PEDF,endostatin Significantly increased(P <0.05 or P <0.01);compared with the model group,the HIF-1α and CD34 MOD of the DBT group decreased(P < 0.05 or P <0.01),and the endostatin MOD increased(P< 0.01);HIF-1α,PDGF m RNA and protein expression levels decreased,and PEDF,endostatin m RNA and protein expression levels increased(P < 0.05 or P < 0.01).Conclusion:1 Qi deficiency,blood stasis and angiogenesis jointly mediate the occurrence of IPF,and angiogenesis is an important pathological link in the presence of Qi deficiency and blood stasis in IPF;2 DBT can be inhibited by regulating the balance of HIF-1α,PDGF,PEDF,and endostatin Angiogenesis,improve the body’s qi and blood running state,thereby delaying the pathological process of IPF.