低氧诱导因子抑制因子在低氧性肺动脉高压中的作用  

Role of Factor Inhibiting Hypoxia-inducible Factor-1 in the Pathogenesis of Hypoxic Pulmonary Hypertension

作　　者：符代炎 戴爱国 胡瑞成 田华 陈云荣 朱黎明 

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 [2]湖南省马王堆疗养院呼吸内科,湖南长沙410016

出　　处：《现代生物医学进展》2015年第22期4263-4267,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(30971329;81270118);湖南省自然科学基金项目(12JJ3111);湖南省中医药科研计划项目(2013138)

摘　　要：目的:研究低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)形成过程中低氧诱导因子抑制因子(factor inhibiting hypoxia-inducible factor-1,FIH)在肺小动脉的表达变化及在HPH发病中的可能作用。方法:将36名患者分为慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)并肺动脉高压组(pulmonary hypertension,PH)组(PH组)、COPD非PH组(COPD组)、对照组,收集肺组织,观察其肺血管重塑指标,原位杂交法与免疫组织化学法检测肺小动脉壁FIH m RNA和蛋白的表达水平。结果:COPD组患者肺小动脉出现血管重塑,PH组患者肺小动脉重塑更明显(P<0.05)。FIH m RNA在各组患者肺小动脉壁的表达无明显差异(P>0.05);FIH蛋白在对照组患者肺小动脉壁高表达,COPD组表达降低,PH组表达进一步减少(P<0.05)。直线相关分析表明,FIH蛋白与FIH m RNA无相关(P>0.05);FIH蛋白与肺小动脉重塑指标、肺动脉收缩压均呈负相关(P<0.01)。结论:慢性肺泡性低氧下调患者肺小动脉壁FIH表达,进而参与患者HPH发病。Objective： To investigate the dynamic expression of factor inhibiting hypoxia-inducible factor-1 （FIH） in the pulmonary arterioles of patients at different phases ofhypoxic pulmonary hypertension （HPH） development, and the role of FIH in the pathogenesis of HPH. Methods： Thirty-six patients were divided into three groups： chronic obstructive pulmonary disease （COPD） with pulmonary hypertension （PH） group （PH group）, COPD without PH （COPD group） and control group. Their lung tissues were collected from surgically resected specimens. The pulmonary arteriole remodeling was observed with morphometric analysis. The expression of Fill in pulmonary arterioles was examined by in situ hybridization and immunohistochemistry. Results： The pulmonary arteriole remodeling was developed in patients from COPD group, and more significantly in patients from PH group （P 〈0.05）. The expression of FIH mRNA remained unchanged in pulmonary arteriole walls between three groups （P 〉0.05）, while the expression of FII-I protein was high in pulmonary arteriole wails in control group, decreased markedly in COPD group and weakened further in PH group （P 〈0.05）. Linear correlation analysis showed that there was no correlation between the FIH mRNA and FIH protein （P〉0.05）. FIH protein was negatively correlated with pulmonary arteriole remodeling parameters and pulmonary artery systolic pressure （P 〈 0.01）. Conclusions： Under chronic alveolar hypoxia, FIH is down-regulated in pulmonary arterioles, and may be involved in the pathogenesis of HPH in patients.

关 键 词：肺动脉高压 低氧 低氧诱导因子抑制因子 肺小动脉 

分 类 号：R563[医药卫生—呼吸系统]