| Aim:To investigate the effect of pretreatment with pravastatin on subsequent ischemia-reperfusion (I/R) injury in rat kidney.Methods:Normal Sprague-Dawley rats were randomized into three subgroups:1) Sham group (n=5);2) I/R group (n=8);3) Pravastatin+I/R group (n=8). I/R injury were induced by clamping both renal arteries for45minutes. Rats were pretreated with pravastatin (20mg/kg/d) for7days before I/R injury and killed24hours later. The effect of pravastatin pre-treatment on subsequent I/R injury was evaluated in terms of renal function (blood urea nitrogen and serum creatinine) and serum lipid profiles (cholesterol and triglycerides). Renal tissues were stained with periodic acid Schiff (PAS) to measure the tubular necrosis and the HSP-70protein expression was measured by immunohistochemistry. TUNEL assay and western blot were used to measure the apoptosis and apoptosis-related protein (Bcl-2, Bax and active caspase-3) expression.Results:Normal rats treated with pravastatin displayed a significant increase in HSP-70expression [(173.9±19.2)%vs (100.9±13.7)%, P<0.01], which mainly located to inner cortex and outer medulla of rat kideys. The I/R group was increased blood urea nitrogen, serum creatinine, tubular necrosis [(36.0±1.2)%vs0, P<0.01] and the number of TUNEL-positive cells [(295.4±28.3) vs (1.4±1.1),P<0.01]to compared to Sham group. In the molecular level, I/R injury significantly inhibited Bcl-2/Bax ratio [(57.3±7.3)%vs(100.0±5.4)%, P<0.01] but increased induced active caspase-3[(385.2±38.7)%vs (96.9±3.1)%, P<0.01] expression. Pre-treatment with pravastatin improved all of above parameters (all P<0.05). Interestingly, there was no significant difference in serum lipid levels between experimental groups.Conclusion:Our findings suggest that the pravastatin prevents against subsequent I/R injury in rat kidney and that this effect is associated with induction of HSP-70independent on its lipid lowering effect. |
PDF Full Text Request