Renoprotective Effects of Emodin in Diabetic Kidney Disease Rats via the NLRP3/GSDMD Signaling Pathway

OBJECTIVE To investigate the effect of emodin on pyroptosis in rat model of diabetic kidney disease(DKD) induced by streptozotocin(STZ), based on the NLRP3/GSDMD signaling pathway.

METHODS The DKD rat model was established via unilateral nephrectomy combined with a single intraperitoneal injection of STZ. Animals were allocated into five groups: control group, model group, emodin 40, 80 mg·kg⁻¹), and NLRP3 inhibitor group(MCC950, 10 mg·kg⁻¹). Renal function parameters were measured before and after treatment. Body weight and blood glucose levels were monitored. Kidney histopathology was evaluated using periodic acid–Schiff(PAS) staining and Masson's trichrome staining to assess renal structural damage and recovery. The mRNA expression of IL-18, IL-1β, HO-1, and NPHS2 was quantified by RT-qPCR. Protein levels of Nephrin, NPHS2, CD2AP, NLRP3, GSDMD, and Caspase-1 were determined by Western blotting.

RESULTS Emodin intervention improved various renal function indicators in DKD rats. Compared with the model group, 80 mg·kg⁻¹ emodin significantly reduced serum creatinine and blood urea nitrogen levels Protein levels of Nephrin, NPHS2, and CD2AP were significantly up-regulated(P<0.05 or P<0.01), while the expression of NLRP3, GSDMD, and Caspase-1 was significantly down-regulated(P<0.05 or P<0.01). Inflammatory factors such as IL-18 and IL-1β decreased(P<0.01 or P<0.001), and the expression of NPHS2 and HO-1 increased to varying degrees(P<0.05 or P<0.01).

CONCLUSION Emodin improves renal function and pathological damage in DKD rats by regulating the NLRP3/GSDMD-mediated pyroptosis signaling pathway.