Puerarin Through The Regulation Of Reactive Oxygen Species On Hypoxia Induced Proliferation Of PAECs

Objective:The pulmonary hypertension induced by hypoxia is a kind of long term exposure to low oxygen environment induced by progressive,complexity,pathological changes,it ultimately lead to irreversible right heart failure,therefore become the difficulty of clinical treatment.Chronic hypoxia leads to intimal hyperplasia of pulmonary artery and disorder of angiogenesis,which is a common histological feature of pulmonary hypertension.Therefore,it is important to study the process of angiogenesis in clinical treatment of pulmonary hypertension.This paper studies the specific mechanisms of platelet source growth factor(PDGF)and vascular endothelial growth factor(VEGF)in regulating pulmonary hypertension.The main role of the exploration is the role of VEGF/VEGFR signaling pathway in the angiogenesis of pulmonary artery endothelial cells.Methods:In the body level experiment,the pulmonary artery model of male Wistar rats induced by hypoxia was established to study the reconstruction and contraction function of the right ventricle(RV).Hemodynamic studies were performed using echocardiography and pressure-volume catheter in rats.In vivo experiments at the same time,adopt Westernblot in vitro technology and Real-timePCR technology used to detect the pulmonary artery endothelial cells in MNRA VEGF protein expression and protein level,to determine whether the PDGF can cause pulmonary hypertension through the regulation of VEGF to participate in a series of complex reaction.The effect of VEGF on cell migration ability was detected by Transwell test,and the effect of VEGF on cell proliferation was detected by Brdu.Flow cytometry is used to detect whether VEGF has an effect on cell mitotic cycle.Results:The results revealed that PDGF receptor-tyrosine kinase inhibitor,imatinib or sunitinib malate,a multi-targeted inhibitor of VEGF receptor and PDGF receptor,both reversed the hypoxia induced right ventricular systolic pressure(RVSP),right ventricular function and thickening of the medial walls,which are characteristic in pulmonary vascular remodeling.Mechanistically,VEGF/VEGFR and PDGF/PDGFR form a biological complex.Meanwhile,we postulated that PDGF-B was the upstream the VEGF/VEEGFR and PDGF-BB directs the regulation of VEGF expression which regulates PAECs proliferation;migration;cell-cycle transition from G0/G1 phase to S phase and G2/M-phase,eventually leading to angiogenesis of PAECs.PDGF has an effect on the proliferation of pulmonary hypertension endothelial cells induced by hypoxia through regulation of VEGF.Conclusion:Hypoxic-induced pulmonary endothelial cell angiogenesis is associated with increased pdgf-bb and VEGF levels,and the increase in VEGF level in this process is regulated by PDGF.