Research On The Protein Expression Of Hypoxia-inducible Factor-1α And Its Regulation Factors In The Lung Tissue Of Newborn Rats With Hypoxic Pulmonary Hypertension

Objective:To know about the protein expression of hypoxia-inducible factor-1α (HIF-1α), endothelin-1(ET-1) and inducible nitric oxide synthase (iNOS) in lung tissue of neonatal rats with hypoxia-induced plmonary hypertension (HPH), and the relationship between these three factors and pulmonary artery pressure or pulmonary vascular remodeling, and to explore the roles of HIF-1α, ET-1and iNOS in the pathogenesis of the disease. Methods:To establish HPH model of newborn rats on day3,5,7,10,14and21after hypoxia, while the control group was set up at each time point of hypoxia.10rats of HPH group and control group were picked up and their mean pulmonary arterial pressure (mPAP) was measured to determine whether the model successfully established at each time point. The morphological change of pulmonary vessels was observed, and pulmonary vascular remodeling indexes were also obtained, including the ratio of middle wall thickness to external diameter of small pulmonary arteries (MT%) and the ratio of media cross-sectional area to total cross-sectional area of small pulmonary arteries (MA%). The protein expression of these three factors in lung tissue was analyzed by Western blot tests. Correlation analysis of these three factors and mPAP, MT%, MA%was done. Results:1. After hypoxia for3,5,7,10,14,21days, the level of mPAP in HPH group was significantly higher than that in control group (P<).05).2.7days after hypoxia exposure, small pulmonary arterials remodeling was observed, further more MT%and MA%in HPH group after hypoxia for7,10,14,21days were significantly higher than those in control group (P<0.05).3. The protein expression of these three factors in lung tissue:(1) The protein level of HIF-la was significantly higher in HPH group after hypoxia for5,7days than that in control group (P<0.05). But after hypoxia for3,10,14,21days, there was no significant difference compared with control group (P>0.05).(2) The protein expression of ET-1was significantly higher in HPH group after hypoxia for3,5,7,10days than that in control group (P<0.05). However, there was no significant difference between HPH group and control group after hypoxia for14,21days (f>0.05).(3) INOS protein level was significantly higher in HPH group after hypoxia for3,5,7days than it in control group (P<0.05). But there was no significant difference between HPH group and control group after hypoxia for14,21days.4. In HPH group, the protein expression of HIF-la was positively correlated with the level of mPAP on the3～21days after hypoxia (P<0.001). The protein expression of ET-1and iNOS was positively correlated with the level of mPAP on the3-7days after hypoxia (P<0.05). However, the protein expression of these three factors had no significant correlation with MT%and MA%(P>0.05). Conclusions:1. Based on preliminary studies, this research further shows that increased protein expression of HIF-la, ET-1and iNOS in lung tissue of newborn rats with HPH is positively correlated with the level of pulmonary artery pressure, so these three factors may play important roles in the pathogenesis of this disease.2. The protein expression of these three factors in lung tissue of HPH neonatal rats increases in the early stage after hypoxia exposure and is no longer increased during the late stage, which indicates that hypoxia tolerance prevailed.