Combination of apigenin and ischemic postconditioning protects against renal ischemia / reperfusion injury in rat by inhibiting TLR 4 / NF-κB signaling pathway

Purpose: To investigate the effect and possible mechanism of combination of apigenin and ischemic post conditioning on renal ischemia-reperfusion injury in rats. Materials and methods: Fifty rats were randomly separated into 5 groups: (1) sham-operation groups: a midline laparotomy was performed only; (2) I/R group: rats were underwent 45 min of renal ischemia; (3) apigenin group: rats was subjected to the same surgical procedures as I/R group, and apigenin was intravenously injected at 10 min prior to the experiment; (4) IPO group: I/R+three cycles of 10 secs of reperfusion and 10 secs of re-occlusion before full reperfusion; (5) apigenin+IPO group: IPO plus the apigenin pretreatment. Rats were sacrificed at 24 hours after I/R injury. Blood samples were collected for the detection of serum creatinine and urea nitrogen levels. Histologic examinations were evaluated. The expression of TLR4, NF-κB, TNF-α, IL-1β and ICAM-1 were performed by immunohistochemistry, Real-time PCR and Western blot. Results: Apigenin and IPO significantly reduced the increase of serum creatinine and urea nitrogen induced by renal ischemia/reperfusion, showing an improvement in renal function. The histologic evidence of renal damage associated with ischemia/reperfusion reduced by apigenin and IPO. Compared with I/R group, the expression of TLR4, NF-κB, TNF-α, IL-1β and ICAM-1 were downregulated by apigenin and IPO on mRNA and protein levels. Conclusions: The combination of apigenin and ischemic postconditioning inhibited TLR4/NF-κB signal pathway in renal ischemia/reperfusion injury, provided remarkable protection against renal ischemia/reperfusion injury in rats.