Effects of sinomenine on expression of HIF-1α and VEGF during renal ischemia-reperfusion in rats

Objective To evaluate the effects of sinomenine on the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) during renal ischemia-reperfusion (I/R) in rats. Methods Fifty-four male Wistar rats, weighing 180-220 g, were randomly divided into 3 groups (n=18 each ) using a random number table: sham operation group (group S), group I/R and sinomenine group (group SIN). Renal I/R was induced by clamping the left renal pedicle for 45 min followed by reperfusion in I/R and SIN groups.In group S, the bilateral renal pedicels were only exposed.Sinomenine 60 mg/kg was intraperitoneally injected at 30 min before reperfusion in group SIN, while the equal volume of normal saline was given in group S and group I/R.At 6, 12 and 24 h (T1-3) of reperfusion, 6 rats from each group were chosen, and blood samples were drawn from the hearts for determination of the serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations.The animals were then sacrificed, and the left kidney was removed and embedded into a paraffin block for determination of the expression of HIF-1α and VEGF in the renal tissues (by immuno-histochemistry). Results Compared with group S, the serum Cr and BUN concentrations were significantly increased at T1-3, and the expression of HIF-1α was significantly up-regulated at T2, 3 in group I/R and group SIN, and the expression of VEGF was significantly up-regulated at T2, 3 in group I/R, and at T1-3 in group SIN.Compared with group I/R, the serum Cr concentration at T1-3 and serum BUN concentration at T2, 3were significantly decreased and the expression of HIF-1α at T2, 3 and VEGF at T1-3 was significantly up-regulated in group SIN. Conclusion The mechanism by which sinomenine attenuates renal I/R injury is related to up-regulation of the expression of HIF-1α and VEGF in the renal tissues of rats. Key words: Sinomenium; Reperfusion injury; Kidney; Hypoxia-inducible factor 1, alpha subunit; Vascular endothelial growth factors