【Animal Modeling】-Study on Serum Metabonomics of Spontaneously Hypertensive Rats with Persistent Hypertension

  Objective To investigate the changes of serum metabolites in spontaneously hypertensive rats (SHR) and the possible related mechanisms.

  Methods Six male SHR and Wistar-Kyoto rats (Wistar-Kyoto rats, WKY) rats were randomly selected as the model and control group respectively. They were reared for 120 days as standard, and BP2000 was used to detect systolic blood pressure (systolic blood pressure) every week. ,SBP). After sampling, the myocardial tissue was stained with HE and Masson; the serum differential metabolites were detected by ultra-high performance liquid mass spectrometry and tandem mass spectrometry (UPLC-MS) method, and further Perform GO and KEGG enrichment analysis.

  Results The SBP of the model group gradually increased, and stabilized after reaching the peak at about 20 weeks of age, and was significantly higher than the control group at each time point (P<0.001); eosin-hematoxylin (hematoxylin-eosin, HE) stained myocardial tissues are arranged disorderly, blood vessel walls are thickened, the lumen is reduced, and homogeneous powdery substances appear in the muscles and around the lumen; Masson stained myocardial tissues can see a large amount of collagen fiber deposition. The serum metabolism pattern and individual difference metabolites showed a clear separation trend between the two groups, and a total of 44 potential marker metabolites were identified, mainly related to the interaction of neuroactive receptor ligands, 5-hydroxytryptamine (5-hydroxytryptamine, 5-HT) Synaptic pathways, arachidonic acid (AA) metabolism and other metabolic pathways.

  Conclusion Persistent hypertension SHR has obvious myocardial and perivascular fibrosis, and its metabolic pattern deviates significantly from normal rats. The serum marker differential metabolites are mainly related to the regulation of sympathetic nerve activity, vasomotor and anti-inflammatory.