Influence And Mechanism Of Feixin Decoction On The Contents Of Expression Of Vascular Endothelial Growth Factor、hypoxia-Inducible Factor-1α And Prolyl Hydroxylase1in Rat Model Of Hypoxic Pulmonary

Background Hypoxic Pulmonary Hypertension(HPH) is consist of earlyvasoconstriction and later the pulmonary vascular remodeling(HPSR)which arecaused by low oxygen vascular endothelial cell injury and vascular endothelialsynthesis and secretion of various vasomotion factor balance disorder.HIF-1plays animportant role in in hypoxia-induced pulmonary arterial smooth muscle cellproliferation.HIF-1a is a functional base of HIF-1,and control many target genesinvolving hypoxia stress to adapt and survive of cells and thus to low oxygen responseon the core role. Low oxygen HIF-1alpha accumulates a lot in the cytoplasm, andmones to the nuclei with dimerization HIF-1βto rasie many kinds of dirty targetgenes expression,such as VEGF which plays the role in the pathogenesis of HPH byinducing cell proliferation and microvascular permeabilith. PHD1promptedhydroxylation of proline residual base of HIF-1αand adjust its stability of oxygen.Feixin Tang reduces pulmonary hypertension which is experience side treating corpulmonale for many years.Objective To explore the effects of Feixin Decoction (FXD) on vascularendothelial growth factor (VEGF)、the hypoxia-inducible factor-1α (HIF-1α) andprolyl hydroxylase domain-containing proteins1(PHD1) in rats model of hypoxicpulmonary hypertension (HPH), and to study its mechanisms for treating HPH.Methods Forty healthy male SD rats were randomly divided into four groups, i.e.,the normal control group, the HPH model group, the FXD group, and the Nifedipinggroup,8rats in each group. The HPH rat model was prepared using normal pressureintermittent hypoxia method. Except the normal control group, rats in the rest groups were fedin a hypoxic plexiglass cabin, with the poor oxygen condition for8h daily for14successive days. Then the distilled water (at30mL/kg) was given by gastrogavage to rats in the normal control group and the HPH model group. FXD (at28g/kg) andNifediping (at20mg/kg) was given by gastrogavage to rats in the FXD group and theNifediping group respectively, once daily, for14successive days. Besides, hypoxiawas continued for14days while medicating. The mean pulmonary artery pressure(mPAP) was detected on the second day after the last medication. The morphology ofthe pulmonary arteriole was detected. The ratio of pulmonary artery wall area andtube area (WA%) and Right ventricular hypertrophy index were determined. Theprotein and mRNA expressions of VEGF、HIF-1α and PHD1in rat pulmonaryarterioles wall were detected using immunohistochemistry and in situ hybridizationtechnique. The protein and mRNA expressions of VEGF、HIF-1α and PHD1in ratlungtissue were detected using Immunohistochemistry and RT-PCR.Results Compared with the normal control group, mPAP、RVHI and WA%,WT%and the protein and mRNA expressions of VEGF and HIF-1alpha in rat pulmonaryarterioles wall and lungtissue significantly increased in the model group (P<0.01),butthe protein and mRNA expressions of PHD1in rat pulmonary arterioles wall andlungtissue significantly decreased in the model group (P<0.01),Compared with theHPH model group, mPAP, RVHI,WA%, LA%and the protein and mRNAexpressions of HIF-1alpha and VEGF significantly decreased in the FXD group(P<0.01). but the protein and mRNA expressions of PHD1in rat pulmonary arterioleswall and lungtissue significantly increased in the FXD group (P<0.01),however,Didn’t return tonormal levels. Compared with the normal control group, RVHI、WA%, LA%and the protein and mRNA expressions of VEGF and HIF-1alpha in ratpulmonary arterioles wall and lungtissue increased in Nifediping group(P<0.01，P<0.05)，the protein and mRNA expressions of PHD1significantly decreased(P<0.01), Compared with the HPH model group， mPAP significantly decreased inNifediping group (P<0.01)，RVHI、WA%and LA%, the protein and mRNAexpressions of VEGF in rat lungtissue, the mRNA expressions of VEGF in ratpulmonary arterioles wall,the protein and mRNA expressions of HIF-1alpha andPHD1in rat pulmonary arterioles wall and lungtissue were no statistical significancein Nifediping group(P＞0.05).the protein expressions of VEGF in rat pulmonaryarterioles wall decreased (P<0.05).Conclusion (1) FXD down-regulated the expression of VEGF through decreasing the expression of HIF-1α. One of its mechanisms for treating HPH might be partiallydue to reversing the remodeling of pulmonary vascular smooth muscle.(2) FXD mightincrease the expression of PHD1to prompte HIF-1α degradation to treat HPH.