低氧诱导因子脯氨酰羟化酶与OS-9在大鼠低氧肺动脉高压中的协同作用  

THE COOPERATION OF OS-9 AND PHDs IN HYPOSIA-INDUCED PULMONARY HYPERTENSION OF RATS

作　　者：潘坤 戴爱国 胡瑞成 

机构地区：[1]湖南省老年医院湖南省老年医学研究所呼吸疾病研究室,湖南长沙410001

出　　处：《中国应用生理学杂志》2009年第1期1-6,共6页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金项目(30570815);教育部科学技术研究重点项目(03091);中国博士后科学基金资助项目(2003033436);湖南省自然科学基金项目(05JJ30073)

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21 d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、Western blot检测蛋白质表达。结果:①HIF-1αmRNA对照组和低氧3 d无明显差异,低氧14 d后表达明显增高;HIF-1α蛋白质低氧3 d组表达明显增高,7 d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14 d下降,低氧21 d保持较低水平;对照组PHD2 mRNA呈阳性表达,低氧3 d增高,14 d达到高峰,21 d维持高水平,其蛋白质表达趋势与mRNA相同;对照组PHD3 mRNA和蛋白质表达不明显,低氧3 d mRNA明显增高,蛋白质低氧3 d明显增高,低氧7 d保持高水平,低氧14 d和21 d下降。③OS-9 mRNA在对照组呈强阳性表达,低氧3 d后迅速降低,14 d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-9 mRNA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。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

关 键 词：低氧诱导因子 低氧诱导因子脯氨酰羟化酶 OS-9 高血压 肺性 低氧 

分 类 号：Q5[生物学—生物化学] Q7