Effect Of Adenovirus Induced HSP70 On Pulmonary Vascular Remodeling, HIF-1a And Its Control Factors In Rats With Hypoxic Pulmonary Hypertension

Objective:To investigate the effect of heat shock protein 70(HSP70) on pulmonary arterial pressure,pulmonary vascular remodeling, HIF-1a,ET-1 and iNOS in neonatal rats with hypoxic pulmonary hypertension(HPH). Methods:According to the random number table method, the 128 wistar neonatal rats were divided into hypoxic group(H) and blank control group(c). Considering the transfection solution, H group was divided into H1:saline group, H2: empty virus group(marked with a green fluorescent signal but did not carry virus vector of target gene), and H3: virus +hHSP70 group(marked with a green fluorescent signal while carrying target gene viral vector).After injection of virus into the H group, the HPH model was established immediately. Then the analysis and comparison of the pulmonary arterial pressure(mPAP),pulmonary vascular remodeling index(MT%?MA%),the expression of HSP70,HIF-1α,ET-1,iNOS of the H group were taken within that of control groups, respectively in hypoxia 3,7,10,14 day. Results:The H1 and H2 groups had more HSP70 protein than C group in 3,7and 10 day of hypoxia, with a significant difference compared with the control group(P<0.01),and the H3 group had more HSP70 protein than other groups(P<0.05).There was no significant difference among four groups in HSP70 from 14 day of hypoxia(P>0.05).On 3,7and 10 day of hypoxia, the mPAP of the H1 and H2 groups kept increasing, with a significant difference compared with the control group C(P<0.05). H3 group did show obvious change, compared with the C group(P>0.05),no statistics meaning. On 14 day of hypoxia,there was no significant difference in mPAP among H1, H2, H3 group(P>0.05), all were significantly higher than that of C group(P<0.05). From 7 day of hypoxia, the H1 and H2 groups had significantly higher MT% and MA% than the control group from(P<0.05), no significantdifference(P>0.05) between H3 group and C group. From 14 day of hypoxia, there was no significant difference in MT% and MA% among H1, H2, H3(P>0.05), and all were significantly higher than that of C group(P<0.05).The H1,H2 and H3 groups had more HIF-a and ET-1protein than C group in 3,7and 10 day of hypoxia, with a significant difference compared with the control group(P<0.01),but H3 group have less HIF-a and ET-1protein than H1 and H2 groups(P<0.01).There was no significant difference among four groups in HIF-a and ET-1 from 14 day of hypoxia(P>0.05).The H1,H2 and H3 groups had more iNOS protein than C group in 3,7and 10 day of hypoxia(P<0.01), H3 group have less iNOS protein than H1 and H2 groups in 3 and 7 day of hypoxia(P<0.01),but there was no significant difference among H1 groupand H2group(P>0.05); H3 group have less iNOS protein than H2 group in 10 day of hypoxia(P<0.01).There was no significant difference among four groups in iNOS from 14 day of hypoxia(P>0.05).Conclusion:Hypoxia stress can induce endogenous HSP70 expression, adenovirus mediated HSP70 can improve the expression of exogenous HSP70 in HPH, downregulate the expression of HIF-1a, ET-1, iNOS, reduce pulmonary arterial pressure, reduce pulmonary vascular remodeling, can become a new strategy for treatment of neonatal HPH.