Abstract
OBJECTIVES: To investigate the therapeutic mechanism of Jianpi Ziren Formula (JPZS) for ameliorating renal injury in mice with systemic lupus erythematosus (SLE). METHODS: Thirty MRL/lpr lupus mice were randomly divided into model group, JPZS treatment group, and prednisone treatment group, with 10 C57BL/6 mice as the control group. After treatment with daily gavage with normal saline, JPZS (7.8 g/kg) or prednisone (5 mg/kg) for 8 consecutive weeks, the mice were examined for changes in serum levels of anti-ds DNA, C3 and Scr, 24-h urine protein (24hPRO) and renal Fe(2+) content, MDA level, SOD activity, GSH level, and ROS level. Renal histopathological changes and ultrastructural changes were observed with HE staining and transmission electron microscopy. The changes in renal expressions of p53, MDM2, GPX4, SLC7A11, ACSL4, Bax, Bcl-2, and caspase-3 mRNAs and proteins were detected using RT-qPCR and Western blotting. RESULTS: Compared with the normal control mice, the mouse models of SLE had significantly elevated levels of dsDNA, Scr, 24hPRO, Fe²⁺, MDA, and ROS, increased renal expressions of p53, MDM2, ACSL4, Bax, and caspase-3, lowered levels of C3, SOD, and GSH, and reduced renal expressions of GPX4, SLC7A11, and Bcl-2 at both the mRNA and protein levels. Treatment with JPZS and prednisone both significantly ameliorated these abnormalities in the mouse models. CONCLUSIONS: JPZS can reduce renal ferroptosis in lupus mice, ameliorate kidney injury, and promote renal function repair possibly by inhibiting the p53-MDM2 signaling axis, which is closely associated with regulation of glomerular podocyte ferroptosis.