VEGF,TGF-β₁Levels And The Effects Of Captopril And Sildenafil Citrate On Them In Juvenile Rats With Right Heart Failure

ObjectiveTo observe the change of vascular endothelial growth factor(VEGF), transforming growth factor beta1(TGF-β1) in serum and VEGF,TGF-β1expression in the right ventricular myocytes of the juvenile rats with right heart failure(RHF), which were induced by monocrotaline(MCT), and the intervention effects of captopril and sildenafil citrate on them.Method784-week-old Sprague-Dawley rats were randomly assigned to two grups:RHF and control.Rats in the RHF group were injected in belly cavity with monocrotaline (MCT). Rats in the control group were injected with9g·L-1’saline in the belly cavity. RHF developed4weeks after an intraperitoneal injection of MCT in the RHF groups.Then rats in the RHF groups were randomly divided into five groups:heart failure4weeks group(group F1),heart failure6weeks group(group F2),captopril group(group C),sildenafil group(group S) and combination group(group C+S).Rats in the control group were randomly divided into normal control4weeks group(group N1)and normal control6weeks group(group N2).The rats in the F1and N1groups were sacrificed at the end of4weeks for observing pathological changes in the myocardium.Group C、group S、group C+S were separately given intragastric administration of captopril(5mg·kg-1·d-1)、sildenafil citrate(10mg·kg-1·d-1)、 captopril(5mg·kg-1·d-1) and sildenafil citrate(10mg·kg-1·d-1) for2weeks.Group F2and N2were given distilled water of equal dose.After2weeks,the rats were sacrificed.Some physiological indexes were measured.Serum VEGF,TGF-β1levels were measured using ELISA. VEGF,TGF-β1protein expression in the right ventricular myocardium was measured by immunhistochemistry.Results1. Right ventricular hypertrophy index[RV/(LV+S)] was significantly higher in the F1group than that in the N1group.The indiscrimindate arrangement of right ventricular myocardium,solution of myoplasm and vacuolar degeneration were observed in F1group,which indicated that the model of right heart failure was successfully formed.2. The levels of serum VEGF and TGF-β1were higher in the F1group than those in the N1group (P<0.05),and there was a positive correlation between the levels of serum VEGF and TGF-β1(r=0.892,P<0.01).3. The synthetic levels of VEGF、TGF-β1in myocardial tissue of the F1group were higher than that of the N1group (P<0.05)4. Compared with the the F1group,the levels of serum VEGF and TGF-β1were higher as well as the synthetic levels of VEGF、TGF-β1in myocardial tissue in the F2group (P<0.05).5. There was a positive correlation between serum TGF-β1levels and myocardial TGF-β1protein expression in the RHF group(r=0.929,P<0.05),which was the same as VEGF(r=0.926,P<0.05).6. As well as the levels of serum VEGF and TGF-β1, the synthetic levels of VEGF、TGF-β1in myocardial tissue of the three drug-treated groups significantly decreased when compared with the F2group (P<0.05). There were no remarkable differences in the levels of serum TGF-β1levels and myocardial TGF-β1protein in right ventricular myocardium among the three drug-treated groups,the same as the VEGF(P>0.05).Conclusion1. VEGF and TGF-β1participated in the development of right heart failure, which were also related to the severity of right heart failure.2. Captopril and sildenafil could have protection for RHF caused by increased pressure load through reducing levels of VEGF and TGF-β1both in the serum and the myocardial tissue of the right ventricular myocardium.The simultaneous use of the2drugs didn’t show any marked curative effect than use any of them.