Study On The Expression Of Hypoxia Inducible Factor-1α In The Pulmonary Artery Smooth Muscle Cell And The Rat Model Of Hypoxic Pulmonary Hypertension

Hypoxia inducible factor-1 α (HIF-1 α ) is a transcription factor which is produced by the body cell exposed to hypoxia condition. HIF-1 a can up-regulate the expression of many hypoxia response genes(HRG) for the body to adapt to hypoxia and maintain the homeostasis. In this experiment, we isolated and cultured the pulmonary artery smooth muscle cell (PASMC) as well as reproduced the rat model of hypoxic pulmonary hypertension. Thus, we observed the expression level of the HIF-1 α and HRG such as VEGF,E-1, PDGF-A in the PASMC and the rat model. The results as follows:(1)On normal oxygen culture condition, the HIF-1 α of PASMC couldn't be detected exsisting. But the VEGF, ET-1 and PDGF-A were found to express in the PASMC.(2)On the hypoxic culture condition (1%O2), the HIF-1 α of PASMC upexpressed gradually. Moreover, the upexpression of HIF-1 α reached the highest at 4h and last for the whole hypoxic condition. The upexpression of HIF-1 a in experiment group is differently higher than in control group (P<0.01). As following the upexpression of HIF-1 α , the expression of VEGF, ET-1 and PDGF-A also increased obviously.(3)When the cyclohexide(inhibitor for protein synthesis) was added to the culture cell, the expression of HIF-1 a obviously decreased (P<0.01,compared to control group) companied with the downexpression of VEGF and ET-1 mRNA, but the downexpression of PDGF-A was not obvious.(4)On the normal oxygen condition, the rat model of hypoxic pulmonaryhypertension couldn't be found to express HIF-1 α . But the VEGF, ET-1 and PDGF-A were discovered by immunohistochemistry.(5)For the rat model of hypoxic pulmonary hypertension, though the HIF-1 α MRNA was not found increasing, the expression of HIF-1 ct protein obviously increased (P<0.01, compared to control group) after the first week of hypoxia condition.And it last for the whole experiment companied with the upexpression of VEGF, ET-1 and PDGF-A. Conclusions:(1)On the normal condition, there isn't HIF-1 α protein in the PASMC while the content of HIF-1 a protein increases on the hypoxia condition.(2)On the hypoxia culture condition, the HIF-1 α of PASMC obviously increases companied with the upexpression of VEGF, ET-1 and PDGF-A. And the transcription of VEGF, ET-1 may be modulated by the HIF-1 α.(3)On the hypoxia condition, PASMC expresses HIF-1 α and it induces the upexpression of VEGF, ET-1. Consequently, the VEGF, ET-1 promote the PASMC to proliferate resulting in the wall of pulmonary artery becoming thick and artery narrow, this may be the incidence mechanism of chronic hypoxia pumouary hypertention.