Metabolomic investigate into the serum of pulmonary hypertension Beagle dogs and the effect of sGC003
10.16438/j.0513-4870.2019-0170
- VernacularTitle:肺动脉高压比格犬血清代谢组学研究及sGC003对其代谢模式的作用
- Author:
Yuan LIU
1
;
Bei YAN
1
;
Xin HU
2
,
3
;
Ai-xin SHI
1
,
3
Author Information
1. Clinical Trial Center, Beijing Hospital, National Center of Gerontology, Beijing 100730, China
2. Department of Pharmacy, Beijing Hospital, Beijing 100730, China
3. Assessment of Clinical Drugs Risk and Individual Application Key Laboratory, Beijing 100730, China
- Publication Type:Research Article
- Keywords:
pulmonary hypertension;
metabolomics;
GC-TOF-MS;
sGC003;
endogenous metabolites
- From:
Acta Pharmaceutica Sinica
2019;54(8):1470-1475
- CountryChina
- Language:Chinese
-
Abstract:
Based on dehydrogenation of monocrotaline-induced Beagle dog model of pulmonary hypertension (PH), GC-TOF-MS metabolomics technique was used to identify potential biomarkers and biologically significant changes in the serum. Pattern recognition method was used for processing metabolomics data to compare PH Beagle dogs (n=11) versus healthy controls (n=8). The results show that 514 compounds were detected in the serum. The profiles of PH models and healthy controls can be distinguished clearly, indicating that there are significant differences in the metabolic profiles. Data analysis revealed 15 types of potential biomarkers, including amino acids glycine and 3-cyanoalanine, glucose, fructose, 1-monopalmitic acid glycerin, and malic acid. Diversified metabolites and their metabolic pathways have been analyzed. We found that different degrees of turbulence and disorganization occurred in glyoxylate and dicarboxylate metabolism, TCA cycle, starch and sucrose metabolism pathways in the Beagle dogs. A soluble guanylate cyclase activator, 4,6-diamino-2-[1-(3-fluorothiophen-2-yl)methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl-N-methyl methyl carbamate (sGC003), was administered (n=15) for comparison with the model and the control. We found that three groups were clearly clustered, indicating that there were differences in the three groups of metabolites. ANOVA statistical analysis results suggested that sGC003 exhibited pharmacodynamic effect, and at the same time, it also changed the endogenous metabolites to some extent. This study laid a foundation for the application of metabolomics in early diagnosis of pulmonary hypertension and provided experimental evidence for the application of sGC003 compound. In this study, the program of animal testing had been approved by Committee on the management of experimental animal in the Beijing Rixin Technology Co. Ltd.
