Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China.
Mol Med Rep. 2017 Dec;16(6):9441-9448. doi: 10.3892/mmr.2017.7801. Epub 2017 Oct 17.
As a typical model of hypoxia‑induced excessive erythrocytosis, high altitude polycythemia (HAPC) results in microcirculation disturbance, aggravates tissue hypoxia and results in a severe clinical outcome, without any effective intervention methods except for returning to an oxygen‑rich environment. The present study aimed to explore potential therapeutic targets which may participate in the recovery of HAPC by studying the mechanisms of reducing the hemoglobin (HB) concentration during re‑oxygenation. A total of 14 and 13 subjects were recruited over a 5,300 m distance and 5,170 m area. The patients were classified into HAPC or control groups based on their HB value. Plasma samples were collected on the day when they finished their stay in plateau for a year, and on the 180th day following their reaching in plain. Metabolic profiling was conducted by UPLC‑QTOF/MS. MetaboAnalyst platform was performed to explore the most perturbed metabolic pathways. A panel of differential metabolites were obtained in the recovery phase of HAPC and control groups. The present study identified the uniquely upregulated pentose phosphate pathway in HAPC subjects, along with a significantly decreased HB level. The findings were verified via a direct comparison between HAPC and control subjects at a high altitude. An increased pentose phosphate pathway was identified in control groups compared with HAPC subjects. An elevated pentose phosphate pathway may therefore participate in the recovery of HAPC, whereas a downregulated pentose phosphate pathway may contribute to hypoxia‑induced erythrocytosis. The results of the present study provide potential therapeutic strategies and novel insights into the pathogenesis of hypoxia‑induced polycythemia.
作为低氧诱导红细胞增多症的典型模型，高原多血症（HAPC）导致微循环障碍，加重组织缺氧，导致严重的临床后果，除了返回富氧环境外，没有任何有效的干预方法。本研究旨在通过研究再氧化过程中降低血红蛋白（HB）浓度的机制，探讨可能参与 HAPC 恢复的潜在治疗靶点。共招募了 14 名和 13 名受试者，在 5300 米的距离和 5170 米的区域内。根据 HB 值将患者分为 HAPC 或对照组。在高原停留一年后和到达平原第 180 天时采集患者的血浆样本。通过 UPLC-QTOF/MS 进行代谢组学分析。使用 MetaboAnalyst 平台探索最受干扰的代谢途径。在 HAPC 和对照组的恢复阶段获得了一组差异代谢物。本研究在 HAPC 受试者中鉴定出独特上调的磷酸戊糖途径，同时 HB 水平显著降低。通过在高海拔地区直接比较 HAPC 和对照组，验证了这些发现。与 HAPC 组相比，对照组中磷酸戊糖途径增加。因此，升高的磷酸戊糖途径可能参与 HAPC 的恢复，而下调的磷酸戊糖途径可能导致低氧诱导的红细胞增多症。本研究的结果为治疗策略提供了潜在的治疗策略，并为缺氧诱导的红细胞增多症的发病机制提供了新的见解。
