Protective Effects Of Tempol On Ischemia/reperfusion Induced Acute Kidney Injury In Mice

Aim:Acute kidney injury(AKI)is a commonly encountered clinical syndrome with a sudden decline in renal function,which may lead to chronic kidney disease,renal failure and death.Free radical scavenger Tempol is a protective antioxidant.In this study,we had observed the effects of Tempol on ischemia/reperfusion(I/R)induced AKI mice and investigated the protective mechanism of Tempol in AKI.Methods:24 health male C57B1/6 mice weighing 25?28 g were randomly divided into three groups:(1)Sham group:mice preformed laparotomy for 30 min;(2)I/R group:one renal pedicle of mice was clamped for 30 min and then reperfusion;(3)Tempol+I/R group:mice were treated with Tempol(50 kg/mg)through intraperitoneal injection 1 h before I/R injury.24 h later the mice were sacrificed and measured the levels of serum creatinine,blood urea nitrogen(BUN)and oxidative stress.Histological changes were observed through periodic acid schiff staining.The expressions of serine/threonine protein kinase(Akt),phosphorylated-Akt(p-Akt),nuclear factor kB(NF-?B),mammalian target of rapamycin(mTOR),phosphorylated-mTOR(p-mTOR),jun N-ter minal kinase,JNK(JNK),phosphorylated-JNK(p-JNK),glycogen synthase kinase-3?(GSK3?),phosphorylated-GSK3?(p-GSK3?),p53 and B-cell lymphoma-2(Bcl-2)were measured through western blot.Responses to Angiotensin II(Ang II)were assessed via measuring vascular diameter by microperfusion of afferent arteriole.Results:(1)Compared with Sham group,the levels of BUN,creatinine,superoxide anion(O2-)and malonyldialdehyde(MDA)increased,superoxide dismutase(SOD)and catalase(CAT)activities decreased,the necrosis of renal tubular epithelial cells increased,the expressions of p-Akt,p-GSK3?,p-mTOR and Bcl-2 downregulated,NF-?B,p-JNK and p53 upregulated,the response of afferent arteriole to Ang II decreased in I/R group.(2)Compared with I/R group,the levels of BUN,creatinine,O2-and MAD decreased,SOD and CAT activities increased,the necrosis of renal tubular epithelial cells decreased,the expressions of p-Akt,p-GSK3?,p-mTOR and Bcl-2 upregulated,NF-?B,p-JNK and p53 downregulated,the response of afferent arteriole to Ang II increased in Tempol+I/R group.Conclusion:Tempol attenuates renal ischemic injury and protects kidney in mice through anti-oxidation,the regulation of PI3K/Akt/mTOR and GSK3? pathways and expression of NK-?B,and enhancing the vascular activity of the afferent arteriole in response to Ang ?.