QiShenYiQi ameliorates salt-induced hypertensive nephropathy by balancing ADRA1D and SIK1 expression in Dahl salt-sensitive rats - 03/09/21
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Abstract |
Background |
Hypertension is a leading risk factor for developing kidney disease. Current single-target antihypertensive drugs are not effective for hypertensive nephropathy, in part due to its less understood mechanism of pathogenesis. We recently showed that QiShenYiQi (QSYQ), a component-based cardiovascular Chinese medicine, is also effective for ischemic stroke. Given the important role of the brain-heart-kidney axis in blood pressure control, we hypothesized that QSYQ may contribute to blood pressure regulation and kidney protection in Dahl salt-sensitive hypertensive rats.
Methods |
The therapeutic effects of QSYQ on blood pressure and kidney injury in Dahl salt-sensitive rats fed with high salt for 9 weeks were evaluated by tail-cuff blood pressure monitoring, renal histopathological examination and biochemical indicators in urine and serum. RNA-seq was conducted to identify QSYQ regulated genes in hypertensive kidney, and RT-qPCR, immunohistochemistry, and Western blotting analysis were performed to verify the transcriptomics results and validate the purposed mechanisms.
Results |
QSYQ treatment significantly decreased blood pressure in Dahl salt-sensitive hypertensive rats, alleviated renal tissue damage, reduced renal interstitial fibrosis and collagen deposition, and improved renal physiological function. RNA-seq and subsequent bioinformatic analysis showed that the expression of ADRA1D and SIK1 genes were among the most prominently altered by QSYQ in salt-sensitive hypertensive rat kidney. RT-qPCR, immunohistochemistry and Western blotting results confirmed that the mRNA and protein expression levels of alpha-1D adrenergic receptor (ADRA1D) in the kidney tissue of the QSYQ-treated rats were markedly down-regulated, while the mRNA and protein levels of salt inducible kinase 1 (SIK1) were significantly increased.
Conclusion |
QSYQ not only lowered blood pressure, but also alleviated renal damage via reducing the expression of ADRA1D and increasing the expression of SIK1 in the kidney of Dahl salt-sensitive hypertensive rats.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | A first report that a compont-based Chinese medicine QiShenYiQi is effective against hypertension. |
• | QSYQ not only lowers salt-induced high blood pressure, but also ameliorates the sequential kidney injury. |
• | Coordinated ADRA1D downregulation and SIK1 upregulation as a mechanism of renal protection by QSYQ. |
Keywords : QiShenYiQi, Salt-sensitive hypertension, Kidney injury, Alpha-1D adrenergic receptor, Salt inducible kinase 1
Plan
Vol 141
Article 111941- septembre 2021 Retour au numéro
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