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Chronic Kidney Disease and Progression

Shen Shuai II recipe improves renal hypoxia to attenuate renal injury in 5/6 renal ablation/infarction rats and effect evaluation using blood oxygenation level-dependent functional magnetic resonance imaging

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Article: 2338565 | Received 22 Nov 2023, Accepted 31 Mar 2024, Published online: 15 Apr 2024
 

Abstract

Background: Renal hypoxia plays a key role in the progression of chronic kidney disease (CKD). Shen Shuai II Recipe (SSR) has shown good results in the treatment of CKD as a common herbal formula. This study aimed to explore the effect of SSR on renal hypoxia and injury in CKD rats. Methods: Twenty-five Wistar rats underwent 5/6 renal ablation/infarction (A/I) surgery were randomly divided into three groups: 5/6 (A/I), 5/6 (A/I) + losartan (LOS), and 5/6 (A/I) + SSR groups. Another eight normal rats were used as the Sham group. After 8-week corresponding interventions, blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) was performed to evaluate renal oxygenation in all rats, and biochemical indicators were used to measure kidney and liver function, hemoglobin, and proteinuria. The expression of fibrosis and hypoxia-related proteins was analyzed using immunoblotting examination. Results: Renal oxygenation, evaluated by BOLD-fMRI as cortical and medullary T2* values (COT2* and MET2*), was decreased in 5/6 (A/I) rats, but increased after SSR treatment. SSR also downregulated the expression of hypoxia-inducible factor-1α (HIF-1α) in 5/6 (A/I) kidneys. With the improvement of renal hypoxia, renal function and fibrosis were improved in 5/6 (A/I) rats, accompanied by reduced proteinuria. Furthermore, the COT2* and MET2* were significantly positively correlated with the levels of creatinine clearance rate (Ccr) and hemoglobin, but negatively associated with the levels of serum creatinine (SCr), blood urea nitrogen (BUN), serum cystatin C (CysC), serum uric acid (UA), 24-h urinary protein (24-h Upr), and urinary albumin:creatinine ratio (UACR). Conclusion: The degree of renal oxygenation reduction is correlated with the severity of renal injury in CKD. SSR can improve renal hypoxia to attenuate renal injury in 5/6 (A/I) rats of CKD.

Acknowledgements

Not applicable.

Authors’ contributions

Research idea and study design: Chen Wang and Yizeng Xu; data curation and formal analysis: Yizeng Xu, Lingchen Wang, and Meng Wang; original draft, review, and editing of the manuscript: Yizeng Xu, Shuohui Yang, Chen Wang, and Chaoyang Ye; visualization and MR scanning: Shuohui Yang and Fang Lu; funding acquisition: Chen Wang and Shuohui Yang. All authors have read and approved the final manuscript.

Ethics approval and consent to participate

The protocol for animal study was approved by the Animal Experiment Ethics Committee of Shanghai University of Traditional Chinese Medicine (PZSHUTCM220725008). All methods were performed in accordance with relevant guidelines and regulations. The study is reported following ARRIVE guidelines.

Consent for publication

Not applicable.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data and materials

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (81973770), the Three Years Action Plan Project of Shanghai Accelerating Development of Traditional Chinese Medicine (ZY[2018-2020]-FWTX-7005), Traditional Chinese Medicine Science and Technology Development Project of Shanghai Medical Innovation & Development Foundation (NO: WL-XJRY-2021006K), the 2023 Jing’ an District Science and Technology Commission and Health and Family Planning System Medical Research Project (2023QT01), Shanghai Municipal Commission of Health and Family Planning Clinical Research Special Project in the Health Care (202340141), and Medical Innovation Research Special Project of the Science and Technology Innovation Action Plan of the Shanghai Municipal Science and Technology Commission (23Y11907600).