*Purpose: To observe the effects of pretreated bortezomib at different points on renal function and renal histology after renal ischemia-reperfusion injury in mice.

*Methods: A mice model of renal ischemia-reperfusion injury was established by clamping the bilateral renal pedicle blood flow for 45 minutes of the male C57BL/6 mice. Mice were randomly divided into saline sham operation group (NS-sham), saline operation group (NS-IRI), bortezomib sham operation group (Btz-sham), bortezomib operation group (Btz-IRI). According to the different injected time of bortezomib, bortezomib in sham operation group and operation group was further divided into 4 days before surgery (Btz-4d-sham/IRI group), 3 days before surgery (Btz-3d-sham/IRI group), 2 days before surgery (Btz-2d-sham/IRI group), 1 days before surgery (Btz-1d-sham/IRI group) and 12 hours before operation (Btz-12h-sham/IRI group). There were 10 mice in each group. Btz-sham group and Btz-IRI group were given a single intravenous injection of bortezomib 0.5mg/kg at different time before the modeling, while NS-sham group and NS-IRI group were given a single intravenous injection of saline 0.5mg/kg at 12 hours before modeling. The serum creatinine (Cr) were observed in 1 days after operation. The changes of renal interstitial inflammatory cells infiltration, necrosis, apoptosis and proliferation of renal tubular epithelial cells were observed by PCR and immunohistochemistry.

*Results: In sham group, bortezomib had no significant effect on serum creatinine, renal tubular epithelial cell necrosis, apoptosis, proliferation and renal interstitial inflammation. In IRI group, compared with the saline operation group, the serum creatinine of mice which were injected bortezomib 12 hours and 1 days before operation increased significantly. The necrosis and apoptosis of renal tubular epithelial cells increased. Renal tubular epithelial cell proliferation and renal interstitial inflammatory infiltration decreased. The serum creatinine of mice which were injected bortezomib 2, 3 and 4 days before operation decreased. Renal tubular epithelial cell necrosis was significantly reduced. There were no significant differences between the apoptosis and proliferation of renal tubular epithelial cells. Renal interstitial inflammatory infiltration decreased.

*Conclusions: The effect of pretreated bortezomib on renal ischemia reperfusion injury was significantly time-dependent. Bortezomib aggravated renal ischemia-reperfusion injury which were injected bortezomib 12 hours and 1 days before operation. This injured effect might be mediated by its inhibition of tubular epithelium proliferation and exacerbation of its apoptosis. However, bortezomib attenuated renal ischemia-reperfusion injury which were injected bortezomib 2 days ,3 days and 4 days before operation. This protective effect might be mediated by its inhibition of renal interstitial infiltration of inflammatory cells.

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