Celastrol Protects Kidney Against Ischemia-reperfusion-induced Injury In Rats

ObjectiveTo investigate the effects and mechanism of celastrol on renalischemia-reperfusion-induced injury in rats.MethodsTwenty-eight male SD rats (250-280g) were randomly divided intoSham group, ischemia reperfusion group (IR group), Low dose group andHigh dose group. Six hours after renal ischemia reperfusion operation, all therats were sacrificed. Serum creatinine (Cr) and blood urea nitrogen (BUN)were measured to indicate the renal function, histologic examination inkidney was assessed by HE staining with a light microscopy,malondialdehyde (MDA) and myeloperoxidase (MPO) activity in kidneywere also measured, TNF-α, IL-1β and MCP-1mRNA were detected byreverse transcription polymerase chain reaction (RT-PCR), the expression ofinflammatory mediators and nucleus and cytoplasm of NF-κB in renal tissuewere detected by IHC and Western blot.Results(1) Compared with Sham group, rats in IR group exhibited a significant increase in both Cr and BUN and showed obvious features of severe acutetubular damage with a higher MDA level (p <0.05); Compared with IRgroup, celastrol markedly decreased the level of Cr and BUN, attenuated thehistologic injury and suppressed oxidative stress induced by IR (p <0.05).(2) Compared with Sham group, the expression of TNF-α, IL-1β,MCP-1mRNA and MPO activity in IR group were notably increased (p <0.05); Compared with IR group, the expression of TNF-α, IL-1β, MCP-1mRNA and MPO activity were obviously lower in celastrol-treated groups(p <0.05).(3) Compared with Sham group, the expression of COX-2,ICAM-1and iNOS in IR group were significantly increased (p <0.05);Compared with IR group, the expression of COX-2, ICAM-1and iNOSwere obviously lower in celastrol-treated groups (p <0.05).(4) Compared with Sham group, the expression of NF-κB protein in IRgroup was reduced in cytoplasm but increased in nucleus (p <0.05);Compared with IR group, the expression of NF-κB protein incelastrol-treated groups was increased in cytoplasm but reduced in nucleus(p <0.05).ConclusionCelastrol significantly reduced IR-induced renal injury in rats with alower level of renal impairment and lipid peroxidation, attenuated the renaltubular damage and down-regulated the expression of TNF-α,IL-1β, MCP-1. Moreover, celastrol inhibited the synthesis of inflammatory mediators,which may be closely associated with the suppression of NF-κB nucleartranslocation. Our results suggested that celastrol may be used for preventingIR-induced renal injury.