Acute Hyperglycemia Worsens And Prevents Dexmedetomidine-induced Preconditioning Against Renal Ischemia-reperfusion Injury In Rats

Acute hyperglycemia is a phenomenon that the blood sugar levels obviously increase due to some reason. Hyperglycemia is an independent factor contributing to the adverse outcomes of renal transplantation, but the specific mechanism is still unclear. Through the establishment of normal SD rat acute hyperglycemia renal ischemic/reper fusion (I/R) model, this research investigated the effects of acute hyperglycemia against renal ischemia-reperfusion injury and tested the effects of acute hyperglycemia on dexmedetomidine-induced preconditioning against renal ischemia-reperfusion injury.Part Ⅰ Acute hyperglycemia aggravates renal dysfunction and the morphological features after renal I/RObjective:We investigatedr the effects of acute hyperglycemia against the renal I/R.Methods:In a normal SD rat acute hyperglycemia renal ischemic/reperfusion (I/R) model, acute hyperglycemia was induced by intraperitoneal injection (i.p.) of 25% glucose (3 g/kg) 45 min before ischemia. Renal warm ischemia was induced by placing a nontraumatic microvascular clamp on the left renal artery and vein for 45 min after right nephrectomy, followed by 24 h reperfusion. The parameters of renal function were determined by biochemical auto-analyzer.Results:The renal dysfunction were significantly aggravated by acute hyperglycemia. Histopathological examination indicated that acute hyperglycemia can aggravate renal I/R injury.Conclusions:These data indicated that acute hyperglycemia can aggravate the renal I/R injury in normal rats.Part Ⅱ Acute hyperglycemia aggravates immune inflammatory injury on renal I/RObjective:To investigate the effect of acute hyperglycemia on immune inflammatory injury in rats with renal ischemia-reperfusion(I/R).Methods:A rat acute hyperglycemia I/R model was established, Renal warm ischemia was induced by placing a nontraumatic microvascular clamp on the left renal artery and vein for 45 min after right nephrectomy, followed by 24 h reperfusion. The concentrations of MPO was measured with spectrophotometer. The concentrations of IL-1β, interferon-y (IFN-y) were measured by immunohistochemistry and RT-PCR methods. The expression of TLR4, TLR2, high-mobility group box 1(HMGB1), Cyclooxygenase 2 (Cox-2) were measured by immunohistochemistry, RT-PCR and Western blot methods.Results:The acute hyperglycemia increased ischemia-reperfusion kidney tissue MPO activity, and obviously increased the level of IL-1β, IFN-y, TLR2 and TLR4, HMGB1, Cox-2.Conclusions:Acute hyperglycemia aggravates immune inflammatory injury on renal I/R.Part III Acute hyperglycemia prevents dexmedetomidine-induced preconditioning against renal ischemia-reperfusion injuryObjective:To investigate the effects of acute hyperglycemia on dexmedetomidine-induced preconditioning against renal ischemia-reperfusion injury.Methods:Sprague-Dawley rats were randomly arranged to the normoglycemic (NG) or hyperglycemic group (HG), with each group further divided into sham (no I/R injury), I/R (ischemia-reperfusion) and dex (given by dexmedetomidine) groups. Acute hyperglycemia was induced by intraperitoneal injection (i.p.) of 25% glucose (3 g/kg) 45 min before ischemia. Dexmedetomidine (50μg/kg, i.p.) was administrated 30 min before induction of ischemia. Renal function, histology, apoptosis, expression of Bax, Bcl-2 and phosphorylated AKT(p-AKT) were detected.Results:I/R insult significantly increased the serum levels of blood urea nitrogen and creatinine, apoptotic tubular epithelial cells, expression of Bax and p-AKT, but decreased Bcl-2 expression. All these changes were further enhanced by hyperglycemia. In hyperglycemic condition, there was no statistically difference between the I/R group and Dex group in all the aforementioned detection indexes.Conclusions:Acute hyperglycemia attenuates dexmedetomidine-induced preconditioning against renal ischemia-reperfusion injury in non-diabetic rats.