血管张力调节剂之间的相互作用导致高原肺水肿和高原居民血管反应性增强。
Interactions among vascular-tone modulators contribute to high altitude pulmonary edema and augmented vasoreactivity in highlanders.
机构信息
Institute of Genomics and Integrative Biology, Delhi, India.
出版信息
PLoS One. 2012;7(9):e44049. doi: 10.1371/journal.pone.0044049. Epub 2012 Sep 11.
BACKGROUND
The interactions among various biomarkers remained unexplored under the stressful environment of high-altitude. Present study evaluated interactions among biomarkers to study susceptibility for high altitude pulmonary edema (HAPE) in HAPE-patients (HAPE-p) and adaptation in highland natives (HLs); both in comparison to HAPE-free sojourners (HAPE-f).
METHODOLOGY/PRINCIPAL FINDINGS: All the subjects were recruited at 3500 m. We measured clinical parameters, biochemical levels in plasma and gene expression using RNA from blood; analyzed various correlations between and among the clinical parameters, especially arterial oxygen saturation (SaO(2)) and mean arterial pressure (MAP) and biochemical parameters like, asymmetric dimethylarginine (ADMA), serotonin (5-HT), 8-iso-prostaglandin F2α (8-isoPGF2α), endothelin-1 (ET-1), plasma renin activity (PRA), plasma aldosterone concentration (PAC), superoxide dismutase (SOD) and nitric oxide (NO) in HAPE-p, HAPE-f and HLs. ADMA, 5-HT, 8-isoPGF2α, ET-1 levels, and PAC were significantly higher (p<0.0001, each), whereas SOD activity and NO level were significantly lower in HAPE-p than HAPE-f (p ≤ 0.001). Furthermore, ADMA, 5-HT, 8-isoPGF2α, NO levels and PAC were significantly higher (p<0.0001), whereas ET-1 level significantly (p<0.0001) and SOD activity non-significantly (p>0.05) lower in HLs than HAPE-f. The expression of respective genes differed in the three groups. In the correlations, SaO(2) inversely correlated with ADMA, 5-HT and 8-isoPGF2α and positively with SOD in HAPE-p (p≤0.009). MAP correlated positively with 5-HT and 8-isoPGF2α in HAPE-p and HLs (p ≤ 0.004). A strong positive correlation was observed between ADMA and 5-HT, 5-HT and 8-isoPGF2α (p≤0.001), whereas inverse correlation of SOD with ET-1 in HAPE-p and HLs (p ≤ 0.004), with 5-HT and 8-isoPGF2α in HAPE-p (p = 0.01) and with 5-HT in HLs (p = 0.05).
CONCLUSIONS/SIGNIFICANCE: The interactions among these markers confer enhanced vascular activity in HLs and HAPE in sojourners.
背景
在高海拔的应激环境下，各种生物标志物之间的相互作用仍未得到探索。本研究评估了生物标志物之间的相互作用，以研究高原肺水肿（HAPE）患者（HAPE-p）和高原居民（HLs）对高原肺水肿的易感性；并与无 HAPE 旅行者（HAPE-f）进行了比较。
方法/主要发现：所有受试者均在 3500 米处招募。我们测量了临床参数、血浆中的生化水平和血液中的 RNA 基因表达；分析了临床参数之间，特别是动脉血氧饱和度（SaO（2））和平均动脉压（MAP）与生化参数之间的各种相关性，如不对称二甲基精氨酸（ADMA）、血清素（5-HT）、8-异前列腺素 F2α（8-isoPGF2α）、内皮素-1（ET-1）、血浆肾素活性（PRA）、血浆醛固酮浓度（PAC）、超氧化物歧化酶（SOD）和一氧化氮（NO）在 HAPE-p、HAPE-f 和 HLs 中的水平。ADMA、5-HT、8-isoPGF2α、ET-1 水平和 PAC 显著升高（p<0.0001，各），而 HAPE-p 中的 SOD 活性和 NO 水平显著低于 HAPE-f（p≤0.001）。此外，ADMA、5-HT、8-isoPGF2α、NO 水平和 PAC 显著升高（p<0.0001），而 ET-1 水平显著（p<0.0001）和 SOD 活性非显著（p>0.05）在 HLs 中低于 HAPE-f。三组的相应基因表达不同。在相关性方面，SaO（2）与 HAPE-p 中的 ADMA、5-HT 和 8-isoPGF2α呈负相关，与 SOD 呈正相关（p≤0.009）。MAP 与 HAPE-p 和 HLs 中的 5-HT 和 8-isoPGF2α呈正相关（p≤0.004）。在 HAPE-p 和 HLs 中，ADMA 与 5-HT、5-HT 与 8-isoPGF2α 之间存在强烈的正相关（p≤0.001），而 SOD 与 ET-1 之间呈负相关，在 HAPE-p 和 HLs 中（p≤0.004），与 5-HT 和 8-isoPGF2α 呈负相关（p=0.01），与 5-HT 呈负相关（p=0.05）。
结论/意义：这些标志物之间的相互作用增强了 HLs 和 HAPE 旅行者的血管活性。
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