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.