论文部分内容阅读
目的通过了解缺氧诱导因子-1α(HIF-1α)、内皮素-1(ET-1)及诱导型一氧化氮合酶(iNOS)的mRNA及蛋白质在缺氧性肺动脉高压(HPH)新生大鼠肺组织中的表达以及和肺动脉压力的关系,探讨三种因子在HPH发病机制中的作用。方法建立HPH新生大鼠模型;分别在缺氧3、5、7、10、14、21天检测平均肺动脉压力(mPAP);通过RT-PCR、免疫组织化学和Western blot方法分别对肺组织中上述三种因子的mRNA、蛋白质表达强度及蛋白质表达量进行分析;进行三因子和肺动脉压力的相关性分析。结果缺氧3、5、7、10天HIF-1αmRNA及蛋白质表达强度均明显高于对照组(P<0.05);缺氧5、7天其蛋白质表达量明显高于对照组(P<0.05)。缺氧3天ET-1mRNA表达明显高于对照组(P<0.05);缺氧3、5、7天ET-1蛋白质表达强度及蛋白质表达量均高于对照组(P<0.05),缺氧10天其蛋白质表达量仍高于对照组(P<0.05)。缺氧3、5、7天iNOS mRNA及蛋白质表达均高于对照组(P<0.05)。缺氧组在缺氧21天内HIF-1α表达总体与mPAP变化呈正相关(P<0.001);缺氧7天内ET-1、iNOS表达总体与mPAP变化呈正相关(P<0.05)。结论 HIF-1α、ET-1和iNOS在HPH新生大鼠肺组织中表达增加,与肺动脉压力呈正相关,三种因子在该病发病机制中可能具有重要作用。
Objective To investigate the effects of hypoxia-inducible factor-1α (HIF-1α), endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) mRNA and protein on hypoxic pulmonary hypertension (HPH) Rat lung tissue expression and pulmonary artery pressure and the relationship between the three factors in the pathogenesis of HPH. Methods HPH neonatal rat model was established. The mean pulmonary arterial pressure (mPAP) was detected on days 3, 5, 7, 10, 14 and 21 after hypoxia. The expression of mPAP in lung tissue was detected by RT-PCR, immunohistochemistry and Western blot, Three factors of mRNA, protein expression and protein expression levels were analyzed; three factors and pulmonary artery pressure correlation analysis. Results The mRNA and protein expressions of HIF-1α at 3, 5, 7 and 10 days of hypoxia were significantly higher than those of the control group (P <0.05). The protein expression of HIF-1α at day 5 and 7 was significantly higher than that of the control group (P <0.05) . The expression of ET-1 mRNA on the 3rd day of hypoxia was significantly higher than that of the control group (P <0.05). The protein expression of ET-1 and the protein expression of hypoxia on the 3rd, 5th, 7th hypoxia were higher than those of the control group (P <0.05) The expression of protein in 10 days was still higher than that in control group (P <0.05). The mRNA and protein expression of iNOS in hypoxia 3, 5 and 7 days were higher than those in control group (P <0.05). In hypoxia group, the expression of HIF-1α was positively correlated with the change of mPAP in hypoxia for 21 days (P <0.001). There was a positive correlation between the expression of ET-1 and iNOS and the changes of mPAP in hypoxia within 7 days (P <0.05). Conclusions The expression of HIF-1α, ET-1 and iNOS in lung tissue of HPH neonatal rats is increased, which is positively correlated with pulmonary artery pressure. The three factors may play an important role in the pathogenesis of HPH.