| AIM: The injury of transplant in early stage induced by Immunological or nonimmunological factors may have an effect on the short and long-term survival of the transplant. Renal ischemia/reperfusion injury is unavoidable in the transplantation process. As an important nonimmunological factor, renal ischemia/reperfusion injury may cause acute inflammatory, significant organ damage or dysfunction, and remains an important problem for kidney transplantation. The warm ischemia time will be longer in the non-heart beating donors. And it has been shown that 30 minutes of warm ischemia is potentially more damaging than 24 hours of cold storage. Our previous in vivo and in vitro studies demonstrated that Yisheng injection (YM), a traditional Chinese medicine, had protective effect on ischemia/reperfusion injury. In this study, we established a model of renal warm ischemia/reperfusion injury in mice. And we have examined whether YM has protective effect for renal warm ischemia/reperfusion injury and explored its protective mechanism.METHODS: Renal warm ischemia/reperfusion was induced in mice. YM at different doses (5, 15, 25 mg/kg) was injected intraperitoneally 12 h and 0.5 h before ischemia. The renal injury, oxidative stress, apoptosis, neutrophil recruitment, proinflammatory mediators and adhesion molecules associated with renal ischemia/reperfusion injury were assayed by enzyme-linked immunosorbent assay (ELISA), immunohistochemical assay and reverse transcription polymerase chain reaction (RT-PCR).RESULTS: Undergoing 50 min of ischemia and 4,24 h of reperfusion caused dramatical injuries in mouse kidneys. Administration of YM at doses of 5,15 and 25 mg/kg effectively reduced serum urea nitrogen and creatinine, from 26.6 ± 1.5 mmol/L and 180.6±6.12 /-imol/Lin IRI group to 15.1±0.63 mmol/L and 94.3±4.26 jumol/L in YM (25 mg/kg) treated group, respectively (PO.01). YM also attenuated necrosis and apoptosis in the tubules of kidneys. Expression of Bcl-2 was up-regulated following IRI. But the expression was much more remarkable in the treatment group. Renal superoxide dismutase (SOD) activity was decreased in all experimental groups compared to sham group and the decrease was much more prominent in untreated group (90.3±2.37 U/mg pro vs. 40.6±2.32U/mg prot, P < 0.01) compared with sham group. YM ameliorated the downregulation of SOD (71.5±1.62 U/mg prot vs. 40.6±2.32U/mg prot, P < 0.01) compared with untreated group. The kidney myeloperoxidase (MPO) and malondialdehyde (MDA) contents were decreased from 15.2 ± 0.83 U/g wet tissue and 180.3±3.92 W mol/L/lOOmg wet tissue in IRI group to 5.6 ± 0.27 U/g wet tissue and 116.3±3.03 jraiol/L/lOOmg wet tissue in YM (25 mg/kg) treated group, respectively (PO.01). Moreover, the serum levels of tumor necrosis factor-alpha (TNF-a) were reduced from 81.2±2.06 pg/ml in IRI group to 20.7 ± 4.24 pg/ml (PO.01). Furthermore, the over-expressions of TNF-a and intercellular adhesion molecule-1 (ICAM-1) were suppressed by YM treatment in a dose-dependent manner.CONCLUSION: YM attenuates renal warm ischemia/reperfusion injury by reducing oxidative stress and suppressing the over-expression of proinflammatory mediators and adhesion molecules.
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