Proteomics reveals the role of in the central regulation of antihypertension by improving the hypothalamus in spontaneously hypertensive rats.

BACKGROUND

In this study, the combination of (EU-TT) was used to intervene in aging spontaneously hypertensive rats (SHRs). Quantitative proteomics sequencing was performed to screen the targets of EU-TT, so as to provide data support for the clinical application of EU-TT.

METHODS

Eighteen-month-old SHRs were administered EU-TT (5.53 g/kg/day) intragastrically for 8 weeks. Blood pressure was recorded to evaluate the efficacy of EU-TT . Transmission electron microscopy (TEM) and hematoxylin-eosin (HE) staining were used to assess the morphology of the hypothalamus. The label free proteomics assay was performed to screen the targets of EU-TT in hypertensive hypothalami. ERK, JNK, and p38 were chosen for Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot.

RESULTS

After 8 weeks of treatment, EU-TT effectively decreased systolic blood pressure (SBP) by 19.2 mmHg and diastolic blood pressure (DBP) by 8.6 mmHg (P<0.05), and improved the hypothalamus morphology of aging SHRs. Label free proteomics identified 248 differentially expressed (DE) proteins (157 were upregulated and 91 were downregulated) in the hypothalamus after EU-TT treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that EU-TT regulated the MAPK signal transduction pathway, which was also confirmed by RT-qPCR and Western blot.

CONCLUSIONS

EU-TT steadily decreased the SBP and DBP of aging SHRs, and improved the morphology of the hypothalamus, which was pharmacologically related to the MAPK signaling pathway.

KEYWORDS

Aging spontaneously hypertensive rats (SHRs); (EU-TT); hypothalamus; label free proteomics; MAPK signaling pathway.