To investigate the effect of curcumin on renal necroptosis in diabetic kidney disease rats.

Adult male Sprague-Dawley (SD) rats were randomly divided into four groups (n=12 per group): a control group, a diabetic kidney disease (DKD) model group (intraperitoneal injection of a single dose of streptozotocin at 55 mg/kg), a DKD model+ curcumin group [daily intraperitoneal injection of curcumin suspension at 200 mg/(kg·d) via intragastric gavage after modeling], and a DKD model + carboxymethyl cellulose sodium (CMC-Na) group (daily intraperitoneal injection of an equal volume of 5% CMC-Na via intragastric gavage after modeling). General conditions of the rats were monitored throughout the study. Urine and blood samples were collected at weeks 8 and 12 to measure 24-h urinary protein, blood glucose, serum creatinine, and blood urea nitrogen (BUN). And bilateral kidneys were harvested for histopathological examination. Furthermore, the protein and mRNA expression levels of tumor necrosis factor-α (TNF-α), receptor-interacting protein 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL), transforming growth factor-β (TGF-β), and interleukin-18 (IL-18) in renal tissues were detected using immunohistochemistry, Western blotting, and qRT-PCR, respectively.

Compared with the control group, rats in the DKD model group and the DKD model+ CMC-Na group exhibited poor general conditions, along with disordered glomerular structure and tubular swelling. Both blood and urinary biochemical indices were significantly elevated (all P<0.01). Furthermore, the expression levels of TNF-α, RIP1, RIP3, MLKL, TGF-β, and IL-18 in renal tissues were also significantly upregulated (P<0.01). Compared with the DKD model+ CMC-Na group, rats in the DKD model + curcumin group showed significant improvement in general conditions and alleviation of glomerular and tubular lesions. Both blood and urinary biochemical indices were significantly decreased (P<0.01). Moreover, the expression levels of TNF-α, RIP1, RIP3, MLKL, TGF-β, and IL-18 in renal tissues were also downregulated (P<0.01).

Curcumin may attenuate renal inflammation and injury in DKD rats by inhibiting TNF-α expression, thereby partially suppressing the activation of the necroptosis pathway and the release of inflammatory cytokines.