| Objective To observe the effects of Feixinning Decoction on the expression of ET-1,ECE,s EPCR and s TM in rats with pulmonary hypertension of cor pulmonale and explore its mechanism of intervention.Methods Ten of fifty male SD rats were randomly selected as the blank group(group A),and the rest rats were injected with monocrotaline(MCT)solution with a concentration of 1%(anhydrous ethanol: normal saline = 2: 8 to fully dissolve monocrotaline in the dark)at a dose of 60mg/kg intraperitoneally for one time,and rat model with pulmonary hypertension of cor pulmonale was established 14 days later.Fifteenth day,the values of mean pulmonary artery pressure(m PAP),pulmonary artery blood flow acceleration time(PAT),pulmonary ejection time(PET),PAT/PET,right ventricular internal diameter(RVID)and right ventricular free wall thickness(RVWT)were detected by two-dimensional echocardiography for model evaluation.After successful modeling,the rats were randomly divided into model group(group B),the Chinese herbal medicine group(group C),the western medicine group(group D),and the Chinese herbal medicine combined with the western medicine group(group E),with 10 rats in each group.Group C was given Feixinning Decoction(8.64g/kg/d)intragastrically;group D was given bosentan(11.25mg/kg/d)intragastrically;group E was given Feixinning Decoction(8.64g/kg/d)and bosentan(11.25mg/kg/d)intragastrically;group A and group B were given 3ml normal saline intragastrically.Each group was administered continuously for 14 days.Twenty-ninth day,after anesthesia,abdominal aortic blood was drawn from rats of each group,and the expression of Endothelin-1(ET-1),soluble Endothelial Protein C Receptor(s EPCR)and Soluble thrombomodulin(s TM)in serum were detected by ELISA;the upper lobe of the right lung was isolated for Hematoxylin-eosin(HE)staining;the middle lobe of the right lung was isolated and used for Western-Blot to detect the expression of Endothelin converting enzyme(ECE);right ventricle(RV),and left ventricle(LV)combined with septum ventriculorum(S)were isolated and weighed to calculate RVHI%.Results1.Behavioural changes of rats: rats in group B showed slow reaction,shortness of breath,some with upward breathing,cyanosis of nose,lips and tongue,dull and dim hair,obvious hair loss phenomenon,and the amount of food intake and drinking water decreased;after treatment,the rats in groups C,D and E showed different degrees of improvement in hair conditions,the color of nose,lip and tongue,breathing and so on,with the most obvious improvement in group E.2.Ultrasonic test results of rats: compared with rats in group A,m PAP and RVWT of rats in group after modeling were increased(P < 0.05);PAT and PAT/PET were decreased(P <0.05);changes in PET and RVID were not statistically significant(P > 0.05).To sum up,the pulmonary artery pressure increased and the right ventricular wall became hypertrophic in rats,which indicated that the model was successful.3.RVHI% results of rats: compared with rats in group A,RVHI% of rats in groups B,C,D and E were increased(P < 0.05);compared with rats in group B,although the changes of RVHI%in groups C,D and E were not statistically significant(P>0.05),they showed a decreasing trend in different degrees.4.HE results of lung tissue in rats: in group B,rats vascular fibrous tissue hyperplasia was observed,with obvious thickening of the tube wall;reduction of the lumen area;disordered arrangement of endothelial cells and partial inflammatory cell infiltration around the tissue.Compared with group B,the rats in groups C,D and E had different degrees of improvement,with the most significant improvement in group E.5.Serum ELISA results of rats: compared with rats in group A,ET-1,s EPCR and s TM expression of rats in group B were increased(P < 0.05).Compared with rats in group B,ET-1,s EPCR and s TM expression of rats in groups C,D and E were decreased(P < 0.05).Among groups C,D and E,ET-1,s EPCR,and s TM expression of rats in group C were the highest,while those in group E were the lowest(P < 0.05).6.Western-Blot results of lung tissue in rats: compared with rats in group A,the ECE expression of rats in group B were increased(P < 0.05).Compared with rats in group B,the ECE expression of rats in groups C,D and E were decreased(P < 0.05).Among groups C,D and E,ECE expression of rats was the highest in group C and the lowest in group E(P <0.05).Conclusion Feixinning Decoction can reduce the expression levels of ET-1,ECE,s EPCR and s TM in rats with pulmonary hypertension of cor pulmonale.It is possible that by regulating the expression of ET-1,ECE,s EPCR and s TM to alleviate the damage of the pulmonary vascular endothelium,restore the endothelial function and play a certain role in regulating pulmonary vascular contraction and remodeling,thus achieving the effect of treating pulmonary hypertension of cor pulmonale.On the basis of bosentan treatment,the combined use of Feixinning Decoction has certain advantages in regulating the expression of ET-1,ECE,s EPCR and s TM in rats with pulmonary hypertension of cor pulmonale,and this provides a basis for the treatment of pulmonary hypertension of cor pulmonale. |
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