Proteomics reveals the role of Eucommia ulmoides-Tribulus terrestris in the central regulation of antihypertension by improving the hypothalamus in spontaneously hypertensive rats

蛋白质组学揭示杜仲-蒺藜通过改善自发性高血压大鼠下丘脑在抗高血压中枢调节中的作用

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作者:Peng Zhang #, Jiacheng Zhang #, Jianlian Wei #, Shuai Feng, Yingzi Qi, Chuanhua Yang, Yuehua Jiang

Background

In this study, the combination of Eucommia ulmoides-Tribulus terrestris (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.

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.

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 in vivo. 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.

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