Irbesartan ameliorates chronic mountain sickness in a rat model via the cholesterol metabolism: An iTRAQ -based proteomics analysis

iTRAQ-based quantitative proteomic analysis of the improved effects of total flavones of Dracocephalum Moldavica L. in chronic mountain sickness

Scientific Reports ◽

10.1038/s41598-021-97091-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Aihaidan Abudouwayiti ◽

Yiliyaer Nijiati ◽

Xiangyang Zhang ◽

Dilinuer Maimaitiyiming ◽

Ainiwaer Aikemu

Keyword(s):

Pulmonary Artery ◽

Pulmonary Artery Pressure ◽

Rat Model ◽

Metabolic Pathways ◽

Quantitative Proteomics ◽

Serum Levels ◽

Chronic Mountain Sickness ◽

Acid Glycoprotein ◽

Artery Pressure ◽

Mountain Sickness

AbstractTo 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.

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The treatment of Uygur medicine Dracocephalum moldavica L on chronic mountain sickness rat model

Pharmacognosy Magazine ◽

10.4103/0973-1296.141817 ◽

2014 ◽

Vol 10 (40) ◽

pp. 477 ◽

Cited By ~ 14

Author(s):

Ainiwaer Aikemu ◽

Xiangyang Zhang ◽

ShiWen Hui ◽

Dilinuer Maimaitiyiming ◽

Guangmei Hu

Keyword(s):

Rat Model ◽

Chronic Mountain Sickness ◽

Mountain Sickness

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Investigation of the Hepato-Protective Effects of Imdur in a Rat Model of Chronic Mountain Sickness

Clinical Laboratory ◽

10.7754/clin.lab.2015.141221 ◽

2015 ◽

Vol 61 (09/2015) ◽

Author(s):

Wanglei ◽

Dilinuer Maimaitiyimin ◽

Yang Tao ◽

Wenhui Shi ◽

Halmurat Upur ◽

...

Keyword(s):

Rat Model ◽

Protective Effects ◽

Chronic Mountain Sickness ◽

Mountain Sickness

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VHL gene methylation contributes to excessive erythrocytosis in chronic mountain sickness rat model by upregulating the HIF-2α/EPO pathway

Life Sciences ◽

10.1016/j.lfs.2020.118873 ◽

2021 ◽

Vol 266 ◽

pp. 118873

Author(s):

Min Yang ◽

Mingming Zhu ◽

Kang Song ◽

Tanna Wuren ◽

Jun Yan ◽

...

Keyword(s):

Rat Model ◽

Gene Methylation ◽

Chronic Mountain Sickness ◽

Vhl Gene ◽

Mountain Sickness

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Effects of chronic normobaric hypoxic and hypercapnic exposure in rats: Prevention of experimental chronic mountain sickness by hypercapnia

International Journal of Biometeorology ◽

10.1007/bf02188924 ◽

1987 ◽

Vol 31 (3) ◽

pp. 201-210 ◽

Cited By ~ 2

Author(s):

B. Lincoln ◽

H. L. Bonkovsky ◽

Lo -Chang Ou

Keyword(s):

Chronic Mountain Sickness ◽

Mountain Sickness

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Global REACH 2018: Volume regulation in high-altitude Andeans with and without chronic mountain sickness

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00102.2021 ◽

2021 ◽

Author(s):

Andrew R. Steele ◽

Michael M. Tymko ◽

Victoria L. Meah ◽

Lydia L Simpson ◽

Christopher Gasho ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Plasma Renin Activity ◽

High Altitude ◽

Glomerular Filtration ◽

Filtration Rate ◽

Plasma Renin ◽

Renin Activity ◽

Chronic Mountain Sickness ◽

Plasma Aldosterone Concentration ◽

Mountain Sickness

The high-altitude maladaptation syndrome known as chronic mountain sickness (CMS) is characterized by polycythemia and is associated with proteinuria despite unaltered glomerular filtration rate. However, it remains unclear if indigenous highlanders with CMS have altered volume regulatory hormones. We assessed N-terminal pro-B-type natriuretic peptide (NT pro-BNP), plasma aldosterone concentration, plasma renin activity, kidney function (urinary microalbumin, glomerular filtration rate), blood volume, and estimated pulmonary artery systolic pressure (ePASP), in Andean males without (n=14; age=39±11) and with (n=10; age=40±12) CMS at 4330 meters (Cerro de Pasco, Peru). Plasma renin activity (non-CMS: 15.8±7.9 vs. CMS: 8.7±5.4 ng/ml; p=0.025) and plasma aldosterone concentration (non-CMS: 77.5±35.5 vs. CMS: 54.2±28.9 pg/ml; p=0.018) were lower in highlanders with CMS compared to non-CMS, while NT pro-BNP was not different between groups (non-CMS: 1394.9±214.3 vs. CMS: 1451.1±327.8 pg/ml; p=0.15). Highlanders had similar total blood volume (non-CMS: 90±15 vs. CMS: 103±18 ml • kg-1; p=0.071), but Andeans with CMS had greater total red blood cell volume (non-CMS: 46±10 vs. CMS 66±14 ml • kg-1; p<0.01) and smaller plasma volume (non-CMS 43±7 vs. CMS 35±5 ml • kg-1; p=0.03) compared to non-CMS. There were no differences in ePASP between groups (non-CMS 32±9 vs. CMS 31±8 mmHg; p=0.6). A negative correlation was found between plasma renin activity and glomerular filtration rate in both groups (group: r=-0.66; p<0.01; non-CMS: r=-0.60; p=0.022; CMS: r=-0.63; p=0.049). A smaller plasma volume in Andeans with CMS may indicate an additional CMS maladaptation to high-altitude, causing potentially greater polycythemia and clinical symptoms.

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