【摘要】：目的：了解缺氧誘導(dǎo)因子-1α（Hypoxia Inducible Factor-1alpha, HIF-1α）及其調(diào)控因子：內(nèi)皮素-1（Endothelin-1, ET-1）、誘導(dǎo)型一氧化氮合酶（inducible Nitric OxideSynthase, iNOS）在缺氧性肺動(dòng)脈高壓（Hypoxia-induced Pulmonary Hypertension,HPH）新生大鼠血清中的含量及肺組織中的表達(dá)水平，探討HIF-1α在新生大鼠HPH發(fā)病機(jī)制中的作用及肺血管重塑隨時(shí)間變化的關(guān)系。方法：建立新生大鼠HPH模型：將120只新生Wistar大鼠隨機(jī)分為HPH組和同日齡常氧對(duì)照組，兩組分別于缺氧3、5、7、10、14、21天取缺氧組及對(duì)照組同日齡新生大鼠各10只測(cè)定其平均肺動(dòng)脈壓（mean Pulmonary Arteria Pressure, mPAP），處死大鼠測(cè)定其右心室肥大指數(shù)（RightVentricle Hypertrophy Index, RVHI），血清HIF-1α、iNOS、ET-1含量及上述基因mRNA在肺組織的表達(dá)水平，測(cè)定血管重塑指標(biāo)MT%、MA%，觀察肺血管超微結(jié)構(gòu)。結(jié)果：（1）缺氧3、5、7、10、14、21天，新生大鼠mPAP持續(xù)增高，，較對(duì)照組有明顯差異（P＜0.05）；（2）缺氧組新生大鼠血清HIF-1α含量在缺氧3、5、7、10、14天明顯高于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05），肺組織HIF-1α mRNA表達(dá)在缺氧3、5、7天明顯高于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）；血清ET-1含量在缺氧3、5、7、10、14、21天均明顯高于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義（P＜0.01），肺組織ET-1mRNA表達(dá)在缺氧3天顯著增高，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）；血清iNOS含量于缺氧3天明顯高于對(duì)照組（P＜0.05），缺氧5、7、10天與對(duì)照組相比差異無(wú)統(tǒng)計(jì)學(xué)意義（P＞0.05），至缺氧14、21天血清iNOS含量低于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）；肺組織iNOS mRNA表達(dá)在缺氧3、5、7天顯著增高，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）；（3）缺氧7天后MT%、MA%、RVHI明顯高于對(duì)照組（P＜0.05），提示出現(xiàn)血管重塑及右心室肥厚。結(jié)論：（1）在新生大鼠HPH的發(fā)生過(guò)程中HIF-1α可能作為核心因子上調(diào)了ET-1及iNOS表達(dá)，致ET-1與NO平衡失調(diào)，在HPH發(fā)生中起了重要的作用。HIF-1α、ET-1及iNOS共同參與了新生大鼠HPH的發(fā)生、發(fā)展；（2）新生大鼠缺氧3~5天肺動(dòng)脈壓力增高，處于肺血管痙攣階段；缺氧7天后肺血管出現(xiàn)重塑，右心肥厚，出現(xiàn)不可逆變化；隨著缺氧時(shí)間延長(zhǎng)，上述變化加劇。
[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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