HIF-1α、ET-1、iNOS在新生大鼠HPH發(fā)病機(jī)制中的作用研究
[Abstract]:Objective: to investigate the content of hypoxia inducible factor-1 偽 (Hypoxia Inducible Factor-1alpha, HIF-1 偽 and its regulatory factors, endothelin 1 (Endothelin-1, ET-1) and inducible nitric oxide synthase (inducible Nitric OxideSynthase, iNOS) in serum and lung tissue of neonatal rats with hypoxic pulmonary hypertension (Hypoxia-induced Pulmonary Hypertension,HPH). To investigate the role of HIF-1 偽 in the pathogenesis of HPH in neonatal rats and the relationship between pulmonary vascular remodeling and time. Methods: the HPH model of neonatal rats was established. 120 neonatal Wistar rats were randomly divided into HPH group and normoxic control group of the same age. The mean pulmonary artery pressure (mean Pulmonary Arteria Pressure, mPAP),) was measured in 10 neonatal rats of the control group and the hypoxia group on the 21st day after hypoxia. The right ventricular hypertrophy index (RightVentricle Hypertrophy Index, RVHI), serum HIF-1 偽, iNOSS-ET-1, and the gene mRNA were measured in the rats of the two groups, the right ventricular hypertrophy index (RightVentricle Hypertrophy Index, RVHI),) and the above gene mRNA were measured in the control group and in the control group respectively on the 21st day after hypoxia. In the lung tissue, The vascular remodeling index (MT%,MA%,) was measured to observe the ultrastructure of pulmonary vessels. Results: (1) the level of serum HIF-1 偽 in neonatal rats in hypoxia group was significantly higher than that in control group (P < 0. 05, P < 0. 05). The content of serum HIF-1 偽 in neonatal rats in hypoxia group was significantly higher than that in control group at 14 days after hypoxia (P < 0. 05), and it was significantly higher than that in control group (P < 0. 05). The expression of HIF-1 偽 mRNA in lung tissue was significantly higher than that in control group on the 7th day after hypoxia (P < 0. 05), and the level of serum ET-1 was significantly higher than that in the control group on the day 1421 after hypoxia (P < 0. 05), and the expression of HIF-1 偽 mRNA in lung tissue was significantly higher than that in the control group on the 7th day after hypoxia (P < 0. 05). The expression of ET-1mRNA in lung tissue increased significantly after 3 days of hypoxia (P < 0. 05). The level of serum iNOS was significantly higher than that of the control group on the 3rd day after hypoxia (P < 0. 05). There was no significant difference between the control group and the control group on the 10th day of hypoxia (P > 0. 05). The serum iNOS content was lower than that in the control group on the day 14: 21 of hypoxia (P < 0. 05). The expression of iNOS mRNA in lung tissue was significantly increased on the 7th day after hypoxia (P < 0. 05); (3). After 7 days of hypoxia, the expression of MT%,MA%,RVHI in lung tissue was significantly higher than that in control group (P < 0. 05), indicating that vascular remodeling and right ventricular hypertrophy appeared. Conclusion: (1) the expression of ET-1 and iNOS may be upregulated by HIF-1 偽 as a core factor in the pathogenesis of HPH in neonatal rats, which leads to the imbalance of ET-1 and NO, and plays an important role in the pathogenesis of HPH. HIF-1 偽, ET-1 and iNOS are involved in the development and development of HPH in neonatal rats. (2) the pulmonary artery pressure increased at the stage of pulmonary vasospasm after hypoxia for 3 days in neonatal rats, the pulmonary vessels were remodeled after 7 days of hypoxia, the right heart was hypertrophy and irreversible changes were found, and the above changes were aggravated with the prolongation of hypoxia time.
【學(xué)位授予單位】:新疆醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2012
【分類(lèi)號(hào)】:R722.1
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