Objective To investigate the mechanism of Bixie Fenqing Pills in improving renal injury caused by hyperuricemia (HUA).
Methods The HUA model rats were induced by gavaging with oxonic acid potassium salt, adenine combined with 10% yeast powder feed for 2 weeks. The model was evaluated based on serum uric acid (SUA) level. The successfully modeled rats were randomly divided into model group, low-dose Bixie Fenqing Pills group, medium-dose Bixie Fenqing Pills group, high-dose Bixie Fenqing Pills group, and febuxostat group, with 8 rats in each group. The drug administration groups were gavaged with the corresponding drugs, while the control group and the model group were gavaged with an equal volume of 0.5% carboxymethyl cellulose sodium (CMC-Na). After 4 weeks of continuous drug administration, the rats were sacrificed for sampling. Biochemical method was used to detect the serum levels of SUA, adenosine deaminase (ADA), xanthine oxidase (XOD), blood urea nitrogen (BUN), and serum creatinine (SCr) in the rats in each group; hematoxylin-eosin (HE) staining was used to observe the pathological changes of renal tissues; the Western blot was used to detect the expression levels of ATP-binding cassette subfamily G member 2 (ABCG2), glucose transporter 9 (GLUT9), and multi-drug resistance-associated protein 4 (MRP4) in renal tissues; immunohistochemistry was used to detect the protein expression levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), and nuclear factor-κB (NF-κB) in renal tissues.
Results HE staining showed that the renal unitstructure in the model group was incomplete, with multiple edema in the renal interstitium, a small number of glomeruli showing atrophy, and incomplete epithelial cells on the glomerular capsule wall; the serum levels of SUA, ADA, XOD, SCr and BUN in the model group were significantly increased (P < 0.01); the expression of GLUT9 protein in renal tissue was upregulated, while the expression levels of ABCG2 and MRP4 proteins were significantly decreased (P < 0.05); immunohistochemical results showed that the expression levels of PI3K, AKT and NF-κB proteins in renal tissues in the model group were increased significantly (P < 0.05). Compared with the model group, Bixie Fenqing Pills could significantly effectively improve renal injuryin HUA rats, reduce serum levels of SUA, ADA, XOD, SCr and BUN, downregulate the expression of GLUT9 protein in renal tissues, and increase the expression levels of ABCG2, MRP4, PI3K, AKT and NF-κB proteins (P < 0.05).
Conclusion Bixie Fenqing Pills may affect the production and metabolism of uric acid by regulating the PI3K/AKT/NF-κB pathway and the expression of uric acid transporter proteins, thereby improving renal injury in HUA rats.
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