Qi-Zhu-Xie-Zhuo-Fang reduces serum uric acid levels and ameliorates renal fibrosis in hyperuricemic nephropathy rats

Hyperuricemia is associated with the development of chronic kidney disease. Epithelial-to-mesenchymal transition (EMT) induced by hyperuricemia is blamed for initiation of renal fibrosis, which is one of the main characters of hyperuricemic nephropathy. Qi-Zhu-Xie-Zhuo-Fang (QZXZF) has been employed clinically for many years to treat patients with hyperuricemic nephropathy, but the mechanism underlying the therapeutic potential remains unclear. In the present study, QZXZF was applied to rats treated with adenine (100 mg/kg) and potassium oxonate (300 mg/kg) and biochemical estimations, morphology and immunohistochemistry were performed to investigate whether QZXZF can improve hyperuricemia induced renal fibrosis and to explore the possible mechanisms. We found QZXZF significantly reduced serum uric acid, cystatinC and hepatic xanthine oxidase (XO) activities, meanwhile improved renal histopathologic changes of hyperuricemic nephropathy rats. Furthermore, QZXZF not only substantially decreased the protein levels of fibronectin and Collagen I but also downregulated E-cadherin and upregulated α-SMA in the kidneys of hyperuricemic nephropathy rats. In conclusion, QZXZF reduced serum uric acid levels and protected kidney against fibrosis in potassium oxonate and adenine induced hyperuricemic nephropathy rats. The mechanism might be associated with the inhibition of hepatic XO activity and the renal epithelial-to-mesenchymal transition.