Objective To investigate the expression of hypoxia inducible factor 1 alpha (HIF 1α) and inducible nitric oxide synthase (iNOS) genes in rats’ pulmonary arteries in different phases of hypoxia induced pulmonary hypertension development Methods Models of chronic hypoxic pulmonary hypertension rat were duplicated by intermittent hypoxia Mean pulmonary arterial pressure (mPAP) was measured by right heart catheterization HIF 1α and iNOS messenger ribonucleic acid (mRNA) were detected by in situ hybridization HIF 1α and iNOS protein were measured by immunohistochemical analysis Results Expression of HIF 1α protein was upregulated in pulmonary arterial tunica intimae of all hypoxic rats In pulmonary arterial tunica media, the level of HIF 1α protein was markedly upregulated at days 3 and 7 of hypoxia ( P <0 01), then tended to restore at 14 days and 21 days HIF 1α mRNA levels in pulmonary arteries of rats began to increase significantly at day 14 of hypoxia ( P <0 01) Expression of iNOS mRNA and protein in pulmonary arteries of rats were upregulated by hypoxia for 3 days ( P <0 01), then reached its peak and maitained the same level while the extension of hypoxia Linear correlation analysis showed that iNOS protein was associated with both mean pulmonary arterial pressure ( r =0 74, P <0 01) and hypoxic pulmonary vascular remodeling ( r =0 78, P <0 01), whereas the inverse was associated with HIF 1α protein ( r =-0 52, P <0 01) Conclusions HIF 1α and iNOS are both involved in the pathogenesis of hypoxia induced pulmonary hypertension in rat HIF 1α protein may upregulate the expression of iNOS gene by transcriptional activation; in addition, iNOS protein may inhibit the expression of HIF 1α protein
骨骼肌功能障碍是慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)的重要组成部分,它包括呼吸肌以及外周非呼吸肌的功能下降,具体表现为:肌肉体积减小,运动强度下降,运动耐力下降。骨骼肌功能障碍严重影响到COPD患者的生活质量及疾病的预后。但是目前COPD的骨骼肌功能障碍发生的具体机制尚不十分明确。研究证实叉形头转录蛋白因子-O(fork head transcr iption factor protein O,FOXO)在维持骨骼肌的功能中具有重要作用。现就COPD患者的骨骼肌障碍与FOXO的关系进行综述。
