To study the protective effect of apigenin (APG) on adriamycin-induced renal injury in rats and explore its mechanism.

Adriamycin nephropathy (AN) model was established by injecting doxorubicin into the tail vein of 60 SD rats, and another 10 rats were given the same volume of vehicle as control group. AN rats were randomly divided into model group, positive control dexamethasone group (DEX group, 0.1 mg·kg^-1·d^-1), APG low-dose group (APL group, 50 mg·kg^-1·d^-1), APG medium-dose group (APM group, 100 mg·kg^-1·d^-1), and APG high-dose group (APH group, 200 mg·kg^-1·d^-1), 10 rats in each group. The rats in DEX and APG groups were given daily intragastric administration, while those in the normal control group and the model group were administered with APG solvent (0.5% CMC-Na solution) for 60 days. The 24-hour proteinuria (PRO), serum renal function, liver function and other biochemical indicators were measured; the pathological examination of the kidney tissue was carried out by HE staining; the CD68 protein in the kidney tissue was marked by immunohistochemistry, and the aggregation of macrophages in the kidney was detected; the apoptosis of renal cells was detected by TUNEL apoptosis assay; the levels of serum inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Lipopolysaccharide (LPS) was used to induce RAW264.7 cell inflammation model, and the inhibitory effect of APG on inflammation at different concentrations was observed; adriamycin was used to induce rat renal tubular epithelial NRK-52E cell injury model, and the effect of APG on cell injury was observed.

Compared with the model group, APM and APH could significantly reduce PRO, plasma total protein (TP), blood urea nitrogen (BUN), and serum creatinine (CRE) contents in the rats after 60 days of treatment, and improve the liver function-related indicators, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the treatment effect of the APH group was better than that of the DEX group; HE staining results showed that APM and APH treatment significantly improved renal tissue lesions; CD68 immunohistochemical and TUNEL apoptosis assay results showed that macrophage aggregation in kidneys of APH group was significantly reduced, cell apoptosis was also improved; the serum levels of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly reduced in the APH group. The above differences were statistically significant (P<0.05, P<0.01, or P<0.001).

APG can improve adriamycin-induced renal injury in rats, which may be related to its anti-inflammatory and cytoprotective effects.