Co-releasing Molecule (CORM-2) Protect Against Renal Ischemia-reperfusion Injury In Mice

Objective To study the protective effects of CO-releasing molecule (CORM-2) on renal ischemia reperfusion injury.Methods Renal IRI was induced by clamping the left renal pedicle for 60 min in uninephrectomized BALB/c mice. 60 mice were divided into three groups randomly: 1)Treatment group, (CORM-2(10ml/kg) in DMSO injected through tail vein 1 hour before renal ischemia); 2)Control group, DMSO instead of CORM-2 injected; Blood and kidney samples were collected after 24 hour of reperfusion. Serum Cr and BUN were determined to assess renal function. HO-1, MPO, TUNEL expression in kidney was detected by immunohistochemistry. Prolongation of renal ischemia time to 80 minutes was undertaken to study the protective effects of CORM-2 on mice mortality.Result The mean serum Cr and BUN levels of the IRI control group were (102.21±42.15)μmol/L and (56.69±15.46) mmol/Lrespectively. Which in CORM-2 treated group were (24.19±9.99)μmol/L and (9.29±4.74) mmol/L. and in Sham group were (18.85±10.24))μmol/l and(8.34±4.00)mmol/l respectively. (CORM-2 vs. IRI control group, P<0.05) and (CORM-2 vs. sham group, P>0.05). CORM-2 treated group significantly improved renal function after ischemia reperfusion. Renal ischemia reperfusion induced obvious pathological changes in the IRI control group,particularly massive tubular infarction and cast formation, In contrast, mice pre-treated with CORM-2 demonstrated significant attenuation of infarction, ischemic glommed and cast connation, however, obvious tubular vacuolization and edema still existed.. The expression of HO-1 in IRI group is far less than CORM-2 group, but is far more than the sham group. The expression of TUNEL in the kidney tissues coped with CORM-2 was significantly weaker than the control group and is similar with sham group. So does with the marker of monocyte MPO. CORM-2 intervention significantly protected mice from lethal kidney ischemia.Conclusion CORM-2 can significantly attenuate kidney ischemia /reperfusion injury, through releasing CO into blood, upregulating the expression of HO-1, and inhibiting the infiltration of inflammatory cells and the renal cells apoptosis.