Objective: In the present study we addressed the ability and the mechanism of simvastatin to reduce ischemia-reperfusion injury (IRI) through up-regulation of heme oxygenase-1 (HO-1) expression. Method: Thirty male SD rats were divided into three groups. Rats in treatment group were given Simvastatin (10 mg ·kg-1 ·d-1)ig 3 days before operation;rats in the control group were given only saline pre-operatively. We induced IRI in these two groups by left renal pedicle clamping for 45 min and performed right kidney resection. Rats in the sham operation group only received right kidney resection. All the animals were sacrificed 24 h after IRI. Blood samples were drawn before the surgery and 24 h after IRI for renal function measurement. Renal morphology and expression of ED-1 and HO-1 were investigated by histological means

immunohistochemistry and Western blot

respectively. Result: Simvastatin pre-treatment reduced quantitative renal damage and attenuated renal dysfunction. Simvastatin treatment increased HO-1 expression on the protein level in the kidney. By immunohistochemistry we identified infiltrating macrophages as the major source for HO-1 expression at 24 h post-ischemia. Conclusion: Simvastatin treatment up-regulates HO-1 in circulating monocytes. The local delivery of HO-1 by infiltrating monocytes/macrophages exerts local anti-inflammatory effects after IRI and thus might reduce tissue destruction.