Research On The Effects Of Adenovirus Induced VEGF-165 On Pulmonary Vascular Remodeling In Neonatal Rats With Hypoxic Pulmonary Hypertension

Objective: To investigate the effect of the overexpression of VEGF on Survivin and pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension(HPH),we observed the expression of the VEGF and Survivin,right ventricular systolic pressure(RVSP)and pulmonary vascular remodeling in the HPH neonatal rats.Methods: Neonatal rats were randomly divided into control group,HPH group and VEGF+HPH group,and each group was further divided into four smaller groups(3rd,7th,10 th,and 14 th day)according to the different observation time.The neonatal rats in the VEGF+HPH group were injected with Ad-VEGF-165-GFP one day before establishing the HPH model with HPH group rats,while the control group rats were exposed to oxygen in the air.Then,neonatal rats in each group were tested for the RVSP.The transfection of adenovirus in lung tissue was observed by immunofluorescence,the expression of VEGF and Survivin in lung tissue was evaluated by immunohistochemical techniques,the pulmonary vascular remodeling was observed under a light microscope,and the pulmonary vascular remodeling index was calculated at different observation time.Results: 1)Immunofluorescence: On the third day after adenovirus transfection in the VEGF+HPH group,gradually decreased green fluorescence was observed in the lung tissue,and it almost disappeared at 14 th day,which suggested that the adenovirus was successfully transfected into the lung tissue of neonatal rats;2)RVSP: Compared with the control group,the HPH group and the VEGF+HPH group had an increase in RVSP since the third day of hypoxia,and the RVSP was gradually increased with the hypoxia time.The HPH group is the highest,the VEGF+HPH group followed.And the differences between every two groups were statistically significant(P < 0.05);3)VEGF: The expression of VEGF in the HPH group increased gradually with time,and the differences from the control group on the 7th,10 th,and 14 th day were statistically significant(P<0.05).However,the VEGF+HPH group showed a gradually decreased expression of VEGF.It was always higher than that of the control group(P<0.05).And the differences between the VEGF+HPH group and the HPH group on the 10 th and 14 th day were not statistically significant(P>0.05);4)Survivin: The expression of Survivin in the HPH group increased gradually with time,but only the difference from the control group on the 14 th day was statistically significant(P<0.05).However,the VEGF+HPH group showed the gradually decreased expression of Survivin,and the difference from the HPH group was not statistically significant(P>0.05);5)Pulmonary vascular remodeling: The HPH group had obvious pulmonary vascular remodeling since the 7th day of hypoxia,and the MT% and MA% were higher than the control group(P<0.05)and increased gradually with the time.While the obvious pulmonary vascular remodeling in the VEGF+HPH group only observed on the 10 th day and 14 th day,and the MT% and MA% were higher than those in the control group(P<0.05).Conclusion: The overexpression of VEGF-165 mediated by adenovirus increased the expression of Survivin,reduced the RVSP,and postponed the pulmonary vascular remodeling,which considered to correlate with the cell survival-promoting function of VEGF and Survivin.