ABSTRACT
@#【Objective】 To investigate the correlations between intestinal flora, plasma metabolites, and blood stasis syndrome in coronary heart disease (CHD), and the mechanisms of Yangxin Tongmai Formula (养心通脉方, YXTMF) for blood stasis syndrome in CHD rats. 【Methods】 A total of 18 specific pathogen free (SPF) male Sqrague-Dawley (SD) rats were used to establish CHD rat models with blood stasis syndrome, which were then randomized into model, YXTMF, and atorvastatin calcium (AVT) groups, with six rats in each group, and were intervened through gavage for two weeks. Subsequently, additional six rats that received normal diet were included as normal group. The pathological changes in the CHD rat models were identified by hematoxylin-eosin (HE) staining. The electrocardiogram, hemodynamics, and lipid profiles of the rats were detected as well. The untargeted plasma metabolomics of rats were analyzed by liquid chromotography-tandem mass spectrometry (LC-MS/MS), their ileal mucosal flora by 16S rRNA sequencing, and the correlation between the two results were also analyzed. 【Results】 The whole blood viscosity, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of rats in the model group increased compared with those in the control group (P < 0.05). In the model group, the proliferation of endothelial cells in the coronary artery of rats was damaged, with quite a few vacuolated pathological changes observed. However, the endothelial lesions in the coronary artery of rats were alleviated in the intervention groups (YXTMF and AVT groups). With the use of LC-MS/MS, a total of 33 potential endogenous metabolites were identified in plasma, among which 1-methylhistidine, N-acetylhistamine, progesterone, and deoxycorticosterone were expected to be the differential metabolites in CHD rats with blood stasis syndrome. The 16S rRNA sequencing results showed that improved diversity and abundance of intestinal flora were observed in the YXTMF group. The correlation analysis suggested that Hydrogenophaga, Limnohabitans, and Polaromonas, which were highly related to the formation of blood stasis syndrome in CHD patients, were positively correlated with plasma metabolites such as 5-hydroxyindole, N-acetylhistamine, and progesterone (P < 0.01), but were negatively correlated with plasma metabolites such as L-arginine, homoarginine, and Boc-beta-cyano-L-alanine (P < 0.01). After YXTMF intervention, Lactobacillus, Corynebacterium, and Candidatus Nitrososphaera were positively correlated with plasma metabolites such as Boc-β-cyano-L-alanine, stachydrine, and naringenin (P < 0.05), while negatively correlated with 5-hydroxyindole, N-acetylhistamine, and oleoylethanolamide (P < 0.05). 【Conclusion】 YXTMF could alleviate blood stasis syndrome in CHD rats through improving their plasma metabolisms achieved by regulating the intestinal flora.
ABSTRACT
@#Abstract: Objective To analyze the plasma metabolomics of patients with occupational silicosis, and screen the differential Methods metabolic pathways in different stages of silicosis. Thirty patients with occupational silicosis were selected as silicosis group by judgment sampling method, including 10 patients in each subgroups with silicosis at stages Ⅰ, Ⅱ, and Ⅲ. Another 10 healthy individuals without occupational dust exposure history were selected as the control group. Plasma of each patientwascollected.Themetabolitesfromtheirplasmasampleswerecollectedandidentifiedbyuntargetedmetabolomicsusing----ultraperformanceliquidchromatographyquadrupoletimeofflightmassspectrometry.Principalcomponentanalysisandpartial least square discriminant analysis were used to compare the differentially expressed metabolites. The metabolic pathways Results enrichment analysis was performed using MetaboAnanlyst 5.0 and other metabolic analysis software. There were significantlydifferentmetabolicprofilesamongtheplasmaofthesilicosissubgroupsandthecontrolgroup.Inthepositivemode,--149differentmetaboliteswerescreened,amongwhich99metaboliteswereupregulatedand50metabolitesweredown regulated. Sphingolipids metabolism, arginine and ornithine metabolism, and fatty acid degradation are the main metabolic pathwaysinsilicosissubgroupswithstagesⅠandⅡcomparedwiththecontrolgroup.Themetabolicpathwaysofsilicosisstage Ⅲ are arginine and proline metabolism, glycerol metabolism, glyoxylic acid and dicarboxylic acid metabolism, and glycine, Conclusion serine and threonine metabolism. The plasma metabolic profile of patients with silicosis in different stages changed significantly. Sphingolipid metabolism is the main metabolic pathway in the early and middle stages of silicosis. In - silicosisterminalstage,thechangeofarginineandproline basedmetabolicpathwayresultinginfibrosisaggravation.
ABSTRACT
The purpose of this study was to systematically analyze the antidepressant mechanism of Chaigui granules from the perspective of biological metabolic network by using integrated metabolomics and biological network analysis tools. The model of chronic unpredictable mild stress (CUMS) depression rat was established, and LC-MS-based plasma metabolomics was used to identify the key metabolites and analyze metabolic pathways underlying the antidepressant effects of Chaigui Granules. The key metabolites regulated by Chaigui granules was integrated with biological network analysis tools to further focus on the key metabolic pathways and explore the potential targets of the antidepressant effect of Chaigui granules. The results showed that there were significant differences in the plasma levels of 20 metabolites in the model group compared with the control group (P < 0.05), Chaigui granules significantly regulated 12 metabolites including docosatrienoic acid, 3-hydroxybutyric acid, 4-hydroxybenzaldehyde, chenodeoxycholic acid, cholic acid, L-glutamine, glycocholic acid, linoleyl carnitine, L-tyrosine, N-acetylvaline, palmitoylcarnitine, arachidonic acid. Further network analysis of the key metabolites regulated by Chaigui granules indicated that plasma arachidonic acid metabolism might be the core pathway for the antidepressant effect of Chaigui granules, with 10 proteins were potential targets for the antidepressant effect of Chaigui granules, including CYP2B6, CYP2E1, CYP2C9, CYP2C8, PLA2G6, PTGS2, ALOX15B, PTGS1, ALOX12 and ALOX5. The animal experimental operations involved in this paper was followed the regulations of the Animal Ethics Committee of Shanxi University and passed the animal experimental ethical review (Approval No. SXULL2020028).