Establishment and Metabolomics Analysis of Rat Model of High-normal Blood Pressure with Excessive Phlegm-dampness Syndrome
10.13422/j.cnki.syfjx.20220460
- VernacularTitle:正常高值血压痰湿壅盛证大鼠模型的建立及代谢组学分析
- Author:
Qiang JIA
1
;
Qiming YIN
1
;
Yunlun LI
1
;
Dongmei QI
1
Author Information
1. Shandong University of Traditional Chinese Medicine （TCM），Jinan 250355，China
- Publication Type:Journal Article
- Keywords:
high-normal blood pressure;
excessive phlegm-dampness syndrome;
animal model;
metabolomics;
liquid chromatography-mass spectrometry technology;
differential metabolites;
metabolic pathways
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(24):171-178
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo construct the rat model of high-normal blood pressure with excessive phlegm-dampness syndrome and analyze the serum metabolites and explain the metabolic characteristics of the model rats. MethodThe model rats of high-normal blood pressure with excessive phlegm-dampness syndrome were fed with high-fat diet and intraperitoneal injected with 7.625 mg·kg-1 of Nω-nitro-L-arginine （L-NNA）， while rats in the normal group were fed chow diet and injected with the same amount of normal saline. The model was evaluated from the aspects of the general state， body weight， blood pressure and serum biochemical indexes， such as triglyceride （TG）， total cholesterol （TC）， high density lipoprotein cholesterol （HDL-C）， low density lipoprotein cholesterol （LDL-C）， blood glucose， malondialdehyde （MDA） and glutathione peroxidase （GSH-Px）. Liquid chromatography-mass spectrometry was used to analyze the changes of metabolites in rats serum. The conditions were as follows：mobile phase of 0.05% formic acid aqueous solution （A）-0.05% formic acid acetonitrile solution （B） for gradient elution （0-3 min， 2%B； 3-9 min， 2%-40%B； 9-18 min， 40%-98%B）， electrospray ionization （ESI）， positive and negative ion detection modes， acquisition range of m/z 80-1 000. Univariate and multivariate statistical analysis were used to screen the differential metabolites between groups which were used to metabolic pathways enrichment analysis. ResultCompared with the normal group， the rats in the model group had the characteristics of darker fur， lazy movement and loose stools， the body weight， blood glucose and contents of TG， TC， LDL-C， MDA increased significantly （P<0.05， P<0.01） and GSH-Px level decreased significantly （P<0.01）， the blood pressure remained stable at about 160/88 mmHg （1 mmHg≈0.133 kPa）. A total of 115 differential metabolites were screened in the positive and negative ion modes， of which 45 were up-regulated and 70 were down-regulated ［variable importance in the projection （VIP） value>1， P<0.05 and fold change （FC）≥2］， including indoleacetaldehyde， 5-hydroxytryptamine， lysophosphatidylcholine， phosphatidylcholine， xanthine and so on， which regulated blood pressure mainly through glycerophospholipid metabolism， linoleic acid metabolism， tryptophan metabolism and arachidonic acid metabolic pathways. ConclusionFeeding with high-fat diet and intraperitoneal injection of L-NNA can successfully construct the rat model of high-normal blood pressure with excessive phlegm-dampness syndrome， and indoleacetaldehyde， 5-hydroxytryptamine， lysophosphatidylcholine， phosphatidylcholine and xanthine can be used as characteristic serum differential metabolites of the rat model.
