ING4、PHDs在低氧性肺动脉高压大鼠中的表达及意义分析

The expression and significanceof ING4 and PHDs in hypoxic pulmonary hypertensive rats

目的对低氧性肺动脉高压大鼠(HPH)中的ING4和PHDs的表达水平及其意义进行探讨。方法利用低氧性肺动脉高压大鼠模型,检测不同缺氧时间点上的大鼠右心室肥大指数(RVHI)、平均肺动脉压(m PAP)以及观察肺小动脉重塑(HPVR)。采用RT-PCR和Western blot检测ING4、PHDs以及HIF-1α的m RNA表达水平及蛋白表达水平。结果结果显示,从缺氧第7天开始实验组大鼠的m PAP显著高于空白对照组(P<0.05),且第14天达到最高值,且大鼠的RVHI也开始增加,且已形成右心室肥厚和官腔狭窄。在m RNA水平上ING4、PHD2以及PHD3的表达在缺氧第3天开始显著增高(P<0.05),且HIF-1α在起初无显著变化直到第14天才开始增高(P<0.05),而PHD1的m RNA表达水平在缺氧后与空白对照组相比,无显著差异(P>0.05);在蛋白水平上ING4的蛋白表达水平在缺氧第7天时表达显著增高(P<0.05),PHD2、PHD3以及HIF-1α的蛋白表达水平在缺氧第3天开始增高(P<0.05),而PHD1的蛋白表达水平在缺氧起初无显著变化,直到第14天时,与空白对照组比较,有显著降低,且随后一直维持较低水平(P<0.05)。结论在低氧性肺动脉高压大鼠中ING4和PHDs的表达变化会影响低氧性肺动脉高压的产生和发展。

Objective To discuss the significance that the Expression of ING4 and PHDs in rats with hypoxic pulmonary hypertension. Methods To detect the value of RVHI、m PAP、HPVR of rat at different hypoxia time points by establishing rat model of hypoxic pulmonary hypertension. Results The m PAP of the experimental group was significantly higher than that of the blank control group（P〈0.05） from the 7th day of hypoxia, and reached the highest value on the 14 th day, and the RVHI of the rats began to increase and formed right ventricular hypertrophy and bureaucratic stenosis. The expression of ING4, PHD2 and PHD3 increased significantly at the 3rd day after hypoxia（P〈0.05）, and HIF-1α did not change significantly at the beginning（P〈0.05）. The expression of ING4 protein was significantly increased at the 7th day of hypoxia（P〈0.05）, PHD2 and PHD3（P〈0.05）, and the protein level of ING4 was significantly higher in the hypoxia group than that in the blank control group（P〈0.05）, and protein expression of HIF-1α increased at day 3 of hypoxia（P〈0.05）, and the protein expression level of PHD1 did not change at the beginning of hypoxia until day 14. Compared with the blank control group,, And then maintained a low level（P〈0.05）. Conclusion The Expression changes of ING4 and PHDs of Hypoxic pulmonary hypertension rats can affect the generation and development of hypoxic pulmonary hypertension.