中文摘要：

目的：研究HIF-1α、PHDs及OS-9的表达变化在低氧性肺动脉高压（HPH）中的作用和意义。方法：SD大鼠随机分5组（n=8）;对照组（C组）和低氧3、7、14和21d组，常压低氧复制HPH大鼠模型。原位杂交、RT-PCR检测mRNA表达，免疫组化、Westernblot检测蛋白质表达。结果：①HIF-1αmRNA对照纽和低氧3d无明显差异，低氧14d后表达明显增高；HIF-1α蛋白质低氧3d组表达明显增高，7d达高峰；②对照组PHD1mRNA呈阳性表达，各低氧组与对照组比较差异不显著，PHD1蛋白质在对照组强阳性表达，低氧14d下降，低氧21d保持较低水平；对照组PHD2mRNA呈阳性表达，低氧3d增高，14d达到高峰，21d维持高水平，其蛋白质表达趋势与mRNA相同；对照组PHD3mRNA和蛋白质表达不明显，低氧3dmRNA明显增高，蛋白质低氧3d明显增高，低氧7d保持高水平，低氧14d和21d下降。③OS-9mRNA在对照组呈强阳性表达，低氧3d后迅速降低，14d达到最低水平；其蛋白质表达趋势与mRNA相同。相关分析表明，肺小动脉壁OS-9蛋白质表达水平与OS-9mRNA呈正相关，与RVHI、mPAP、WA％及LA％呈负相关。结论：HIF-1α、PHDs及OS-9均在大鼠HPH的发病机制中发挥作用。OS-9可能通过增强PHDs的活性来调节HIF-1α的表达，从而在HPH的发生和发展中发挥作用。

英文摘要：

Aim： To investigate the dynamic expression of hypoxia-inducible factor 1α, PHDs and OS-9 in pulmonary arteries of rats with hypoxia-in duced pulmonary hypertension. Methods： SD rats were randomly divided into 5 groups （ n = 8） and exposed to hypoxia for 0, 3, 7, 14 or 21 d, respectively. RT-PCR and in situ hybridization were used to determine the expression of mRNA. Immanohistochemistryand Western blot were used to detemaine the expression of protein. Results： HIF-1α protein was poorly positive in control, markedly up- regulated after 3 d and 7 d of bypoxia（ P 〈 0.05, vs group C）, and then declined slightly after 14 d and 21 d of hypoxia. HIF-1α mRNA increased dramaticly after 14 d of hypoxia（ P 〈 0.05, vs group C）. PHD1, PHD2 mRNA and protein was positive in group C. PHD2 mRNA and protein were up-regu- lated after 3 d of hypoxia（ P 〈 0.05, vs group C）, reaching its peak after 14 d of hypoxia while PHD1 protein declined after 14 d of hypoxia （ P 〈0O. 05, vs group C） without statistic mRNA changing. PHD3 mRNA and protein were detected at low level in control, markedly up-regulated after 3 d of hypoxia（ P 〈 0.05, vs group C）, and then PHD3 mRNA kept at high level while PHD3 protein declined after 14 d of hypoxia （ P 〈 0.05, vs 7 d）. OS-9 mRNA was positively in control, markedly decreased after 3 d of hypoxia（ P 〈 0.05, vs group C）, reaching its lowest lever after 14 d of hypoxia. Linear correlation analysis showed that OS-9 protein was positively correlated with OS-9 mRNA（ r = 0.82, P 〈 0.01 ） and HIF-1α protein（ r = 0.57, P 〈 0.01 ）. Conclusion： HIF-1α, PHDs and OS-9 are all involved in the pathogenesis of hypoxic pulmonary hypertension in rats. OS-9 may interact with both HIF-1α and PHDs to promote PHD-mediated hydroxylation of HIF-1α