Protective Effects Of Octreotide On Renal Ischemic-reperfusion Injury And Mechanism

Objective Oxidative stress,calcium overload,inflammation,cellular necrosis and apoptosis are implicated in the renal ischemia/reperfusion injury(RIRI).Since octreotide(OCT)is protective in retina IRI,the effect of OCT on mouse RIRI and the mechanisms involved were investigated.Methods Twenty-four mice were randomly divided into three groups(n=8)using randomized number table method:(I)sham group;(?)RIRI group;(III)RIRI+OCT treatment(RIRI+OCT)group.The RIRI+OCT group mice were treated with injection of OCT(dissolved in sterile saline)30 ?g/kg twice/day subcutaneously after completion of the ischemic condition.Sham and RIRI group mice received the same volume of isotonic saline.The renal ischemia-reperfusion model was established in group RIRI and group RIRI+OCT.Twenty-four hours after RIRI,serum and tissues from these mice were collected.The levels of serum creatinine(SCr)and blood urea nitrogen(BUN)were measured.The renal injury was observed by distribution of periodic acid-Schiff(PAS)staining.The apoptotic cells in kidney tissues were measured using a terminal deoxynucleotidyl transferase dUTP nick end labelling(TUNEL)assay.Levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-a in kidney tissues were detected using commercial ELISA kits;The content of malondialdehyde(MDA)and reactive oxygen species(ROS)were tested as well as the activities of superoxide dismutase(SOD).The levels of nuclear factor(NF)-?B,nuclear factor erythroid 2-related factor(Nrf)2,heme oxygenase(HO)-1 and NAD(P)H quinone oxidoreductase(NQO)-1 protein in renal tissues were detected using western blot and immunohistochemical(IHC)staining.Results:All mice in the three groups were survived 24 h after the surgery.Treatment with OCT restored the renal functions and histological changes induced by RIRI.The administration of OCT reduced the TNF-a and IL-6 levels in kidney tissues,protected the kidney from apoptosis and significantly downregulated the expression of nuclear NF-?B.Additionally,OCT treatment upregulated the expression of Nrf2,HO-1 and NQO1 and enhanced the renal antioxidant capacity.Conclusion OCT may protect renal from IRI,which could be through up-regulation of Nrf2 signaling pathway and down-regulation of NF-?B.