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A Study On The Mechanism Of Intervention Of Feixinning Decoction In Rats With Right Heart Failure Due To Pulmonary Arterial Hypertension Through Regulation Of VEGF And TGF-β1

Posted on:2023-02-03Degree:MasterType:Thesis
Country:ChinaCandidate:X LiangFull Text:PDF
GTID:2544306845971189Subject:Chinese medical science
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Objective:By copying pulmonary arterial hypertension induced by right heart failure rat model,to investigate the effects of Feixinning Decoction on the expression levels of VEGF and TGF-β1,and its protective effect on the myocardium of right heart failure induced by pulmonary hypertension.Methods:Male SD rats were intraperitoneally injected with monocrotaline(MCT)to establish a model of right heart failure induced by pulmonary hypertension.Two-dimensional echocardiography was performed 4 weeks later to detect the model.And they were divided into blank control group(group A),MCT model group(group B),Fexinning high-dose group(group C),Fexinning medium-dose group(group D)and Fexinning low-dose group(group E)by random number table method,with 20 birds in each group,100 birds in total.From the 5th week,groups A and B were given equal volume of normal saline intragastrically,while groups C,D and E were given1.08g/kg,0.54g/kg and 0.27g/kg Fexinning solution by clinical equivalent dose,once A day,and samples were taken after 2 weeks of intragastrically.(1)Observe and record the general condition and death of rats;(2)2D echocardiography for pulmonary artery pressure and basic cardiac function;(3)morphology of myocardial tissue by HE staining;(4)VEGF and TGF-β1 in serum by ELISA;(5)protein expression of VEGF and TGF-β1 by Western blot;(6)statistical analysis by SPSS22.0 software.Results:1.General condition and death of rats:Compared with group A,group B rats had short of breath,depression,unresponsive,cyanosis of lips and extremities,reduced eating,irritable,and high mortality.Compared with group B,the rats in groups C,D and E were significantly improved in mental aspects,respiratory status,fur color,diet and drinking,etc.and group C was the most significant.The mortality rate decreased significantly,especially in groups C and D.2.Pulmonary artery pressure related indicators:Compared with group A,the pulmonary artery pressure(P),pulmonary artery blood flow velocity(V)and the ratio of pulmonary artery pressure to velocity(P/V)in group B were significantly increased(P<0.05);PA-AT,ET and PA-AT/ET were significantly decreased(P<0.05),suggesting that the establishment of pulmonary hypertension rat model was successful.3.Cardiac ultrasound results:Compared with group A,the right atrial inner diameter(RA)and right ventricular inner diameter(RV)of group B were significantly increased(P<0.05),heart rate(HR)was increased(P<0.05),stroke volume(SV)and ejectionfraction(EF)were decreased(P<0.05).Left ventricular internal dimension diastole(LVIDd),end-diastolic volume(EDV)and left ventricular internal dimension systole(LVIDs)increased in diastolic period(P<0.05),suggesting pathological changes of right heart failure in rats with pulmonary hypertension.4.HE staining results of myocardial tissue:There were no obvious pathological changes in myocardial tissue of rats in group A.In group B,myocardial tissue was abnormal,the arrangement of myocardial cells was loose,and a large number of inflammatory cells could be seen in the interstitium.After the fexinning decoction intervention,compared with group B,the pathological morphology of heart tissue in groups C,D and E was improved to varying degrees,with reduced infiltration of myocardial inflammatory cells and orderly arrangement of myocardial cells,especially in group C.5.Serum VEGF and TGF-β1 ELISA results:The serum VEGF and TGF-β1contents of rats in group A did not change significantly.Compared with group A,The serum VEGF and TGF-β1 contents in group B were significantly higher than those in group A(P<0.05).After the intervention,the contents of VEGF and TGF-β1 in serum in groups C,D and E were significantly lower than those in group B(P<0.05).The serum VEGF and TGF-β1 contents in group C were significantly lower than those in groups D and E(P<0.05).6.VEGF and TGF-β1 Western blot results: No protein expression of VEGF and TGF-β1 was changed in group A rats.Compared with group A,the protein expression of VEGF and TGF-β1 in group B rats was significantly higher in the myocardial tissue(P<0.01).After fexinning intervention,compared with group B,the protein expressions of VEGF and TGF-β1 in myocardium tissues of groups C and D were significantly decreased(P<0.01),while VEGF was decreased in group E(P<0.05),and there was no statistical significance in TGF-β1 in group E(P>0.05).Compared with group E,the protein expressions of VEGF and TGF-β1 in groups C and D were significantly decreased(P<0.01).Conclusion:Fexinning Decoction can reduce pulmonary artery pressure and inhibit right ventricular remodeling,and has protective effect on rats with right heart failure caused by pulmonary artery hypertension.Fexinning high-dose group has a significant effect,and its mechanism maybe related to the regulation of VEGF and TGF-β1.
Keywords/Search Tags:Pulmonary arterial hypertension, Right heart failure, Fexinning decoction, VEGF, TGF-β1
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