QiShenYiQi ameliorates salt-induced hypertensive nephropathy by balancing ADRA1D and SIK1 expression in Dahl salt-sensitive rats.

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.

• Authors: Hongxia Du, Guangxu Xiao, Zhifeng Xue, Zhixiong Li, Shuang He, Xiaoli Du, Zhengchan Zhou, Linghua Cao, Yule Wang, Jian Yang, Xiaoying Wang, Yan Zhu
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 141 Pg. 111941 (Sep 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 34328102 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Adra1d protein, rat
• Drugs, Chinese Herbal
• Receptors, Adrenergic, alpha-1
• Sodium Chloride, Dietary
• qishen yiqi
• Protein Serine-Threonine Kinases
• Sik1 protein, rat

Topics

• Animals
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Gene Expression
• Hypertension, Renal (drug therapy, metabolism)
• Male
• Nephritis (drug therapy, metabolism)
• Protein Serine-Threonine Kinases (biosynthesis)
• Rats
• Rats, Inbred Dahl
• Receptors, Adrenergic, alpha-1 (biosynthesis)
• Sodium Chloride, Dietary (toxicity)