The First Affiliated Hospital of Xinjiang Medical University, No. 1, Liyushan Road, Xinshi District, Urumqi, 830054, Xinjiang, China.
Central Laboratory of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China.
Sci Rep. 2021 Sep 1;11(1):17526. doi: 10.1038/s41598-021-97091-z.
To use isobaric tags for relative and absolute quantification (iTRAQ) technology to study the pathogenesis of chronic mountain sickness (CMS), identify biomarkers for CMS, and investigate the effect of total flavones of Dracocephalum moldavica L. (TFDM) on a rat model of CMS. We simulated high altitude hypobaric hypoxia conditions and generated a rat model of CMS. Following the administration of TFDM, we measured the pulmonary artery pressure and serum levels of hemoglobin (Hb), the hematocrit (Hct), and observed the structure of the pulmonary artery in experimental rats. Furthermore, we applied iTRAQ-labeled quantitative proteomics technology to identify differentially expressed proteins (DEPs) in the serum, performed bioinformatics analysis, and verified the DEPs by immunohistochemistry. Analysis showed that the pulmonary artery pressure, serum levels of Hb, and the Hct, were significantly increased in a rat model of CMS (P < 0.05). Pathological analysis of lung tissue and pulmonary artery tissue showed that the alveolar compartment had obvious hyperplasia and the pulmonary artery degree of muscularization was enhanced. Both pulmonary artery pressure and tissue morphology were improved following the administration of TFDM. We identified 532 DEPs by quantitative proteomics; gene ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis further revealed that metabolic pathways associated with coagulation and complement play crucial roles in the occurrence of CMS. Immunohistochemistry verified that several DEPs (α-1-acid glycoprotein, collagen, fibulin, haptoglobin, PLTP, and TAGLN2) are important biological markers for CMS. Our analyses demonstrated that TFDM can improve CMS and exert action by influencing the metabolic pathways associated with coagulation and complement. This process relieves pulmonary artery pressure and improves lung function. We also identified that α-1-acid glycoprotein, collagen, fibulin, haptoglobin, PLTP, and TAGLN2 may represent potential biomarkers for CMS.
为了使用同位素质谱标签相对和绝对定量（iTRAQ）技术来研究慢性高原病（CMS）的发病机制，鉴定 CMS 的生物标志物，并研究Dracocephalum moldavica L.总黄酮（TFDM）对CMS 大鼠模型的影响。我们模拟高原低氧环境，建立 CMS 大鼠模型。给予 TFDM 后，测量肺动脉压和血红蛋白（Hb）、红细胞压积（Hct）水平，并观察实验大鼠肺动脉结构。此外，我们应用 iTRAQ 标记定量蛋白质组学技术鉴定血清中差异表达蛋白（DEPs），进行生物信息学分析，并通过免疫组化验证 DEPs。分析表明 CMS 大鼠模型中肺动脉压、血清 Hb 和 Hct 水平显著升高（P<0.05）。肺组织和肺动脉组织病理分析显示肺泡腔明显增生，肺动脉肌化程度增强。TFDM 给药后肺动脉压和组织形态均得到改善。通过定量蛋白质组学鉴定了 532 个 DEPs；GO 和 KEGG 通路分析进一步表明，与凝血和补体相关的代谢途径在 CMS 的发生中起着关键作用。免疫组化验证了几个 DEPs（α-1-酸性糖蛋白、胶原、纤连蛋白、触珠蛋白、PLTP 和 TAGLN2）是 CMS 的重要生物标志物。我们的分析表明，TFDM 可以通过影响与凝血和补体相关的代谢途径来改善 CMS 并发挥作用。这一过程缓解了肺动脉压，改善了肺功能。我们还发现，α-1-酸性糖蛋白、胶原、纤连蛋白、触珠蛋白、PLTP 和 TAGLN2 可能是 CMS 的潜在生物标志物。
