中文摘要：

目的研究慢性阻塞性肺疾病（COPD）患者肺动脉高压形成过程中Siah表达变化的规律及与PHDs和HIFs—α的相关关系。方法HE染色检测COPD患者和对照组患者肺小动脉形态学改变，应用原位杂交检测肺小动脉壁内Siah、PHDs及HIFs—αmRNA的表达水平，应用免疫组织化学检测肺小动脉壁内Siah、PHDs及HIFs—α蛋白质表达水平。结果COPD患者肺小血管HIFs—αmRNA和蛋白质表达均增高，蛋白质增高更明显，COPD患者PHDlmRNA与对照组比较差异无统计学意义，PHD2、PHD3mRNA表达明显增高，PHD1蛋白质表达水平降低，PHD2蛋白质水平升高，PHD3较对照组比较差异无统计学意义。COPD组Siahl和Siah2蛋白质与mRNA的表达均有升高，与对照组比较差异有统计学意义。直线相关分析表明，Siam、Siah2蛋白质与HIFs—α蛋白质呈正相关。结论COPD患者中Siahl与Siah2可能通过泛素-蛋白酶体途径在转录后水平对PHDs的蛋白稳定性进行调节，间接对HIFs起正调控作用。

英文摘要：

Objective To investigate the dynamic levels of Siah in chronic obstructive pulmonary disease （COPD） patients and the correlation relationship among Siah, prolyl hydroxylase domain- containing proteins （PHDs） and hypoxia-inducible factor alpha （HIFs-α） during the development of hypoxia pulmonary hypertension （HPH）. Methods Small pulmonary arterial remodeling was observed in COPD and the control patients by morphometric analysis. The expression of Siah, PHDs and HIFs-α in lung tissue was examined in COPD patients and the control by in situ hybridization and immunohistochemistry. Results In COPD subjects, HIFs-α mRNA and proteins increased significantly, PHD1 protein decreased without mRNA change increased significantly. PHD3 mRNA increased without protein changes. Siam and Siah2 mRNA and protein increased. Siah2 showed the same dynamic tendency with Siahl. Linear correlation analysis showed that Siah protein were positively correlated with HIFs-α protein. Conclusions Siam and Siah2 may target PHDs for proteasome-dependent degradation in rat lung after hypoxia exposure and therefore resulted in HIFs-a accumulation.