Exploring the Protective Effect and Regulatory Mechanism of Plumbagin on Renal Ischemia-Reperfusion Injury Based on the Nrf-2/HO-1 Signaling Pathway.

Objective: To investigate and validate the protective role of plumbagin (PL) in renal ischemia-reperfusion injury (IRI) by mediating the Nrf2/HO-1 pathway and reducing renal function damage, thereby providing a theoretical basis for the application of PL in the prevention of renal IRI.

Methods: Twenty-four healthy adult male BALB/c mice were randomly divided into four groups: the sham group, the IR model group (IRI group), the IRI + PL 10 mg/kg group, and the IRI + PL 10 mg/kg + ML385 (30 mg/kg) group. Four groups of mice were given drugs 2 weeks before modeling, for 2 consecutive weeks (once a day), and the modeling was started 1 hour after the administration on the 14th day. In the sham operation group, only the renal vessels were isolated without clamping ischemia, and in the other groups, minimally invasive artery clamps were used to establish the mouse RIRI injury model. Serum creatinine (Scr), blood urea nitrogen (BUN), interleukin-6 (IL-6), myeloperoxidase (MPO), serum superoxide dismutase (SOD), GSH-Px, malondialdehyde (MDA), and inflammatory levels of mice in each group were detected and analyzed; pathological examination of renal tissue injury; and the expressions of Nrf-2 and HO-1 were detected by Western blotting.

Results: Compared with the sham group, the IRI group showed elevated Scr, BUN, IL-6, MDA, and MPO levels, reduced SOD and GSH-Px activities, severe renal injury, and decreased Nrf-2/HO-1 expression. PL administration reduced renal injury, decreased Scr, BUN, IL-6, MDA, and MPO levels, increased SOD and GSH-Px levels, and increased Nrf-2/HO-1 expression, as confirmed by pathology and Western blotting.

Conclusions: PL can reduce the level of oxidative stress and the release of inflammatory factors by regulating the Nrf-2/HO-1 signaling pathway, improve renal injury induced by ischemia/reperfusion in mice, and play a renoprotective role.