Protective Effect And Mechanism Of Isoacteoside On LPS-Induced Acute Renal Injury Associated With Sepsis

Objective:To investigate the protective effect of Isoacteoside(IAC)on kidney injuries and the possible mechanisms in mice with kidney injury induced by lipopolysaccharide(LPS),to provide the experimental basis for the clinical treatment of acute renal injury.Methods:For AKI model,Sixty mice were randomly divided into six groups:control group,LPS group(10mL·kg-1,i.p.),IAC(50,100,200mL/kg,i.p.)group and positive control dexamethasone group(5mL·kg-1,i.v.),and 10 mice per group.In IAC groups,the mice of were injected with IAC(50,100,200mL/kg,i.p.)at 3h before LPS injection,and injection at 3h and 6h after LPS injection.In dexamethasone groups,mice were injected with dexamethasone at 1h before LPS injection.After 12h,observed the general survival statethe of mice,the mice renal weight index of each group were measured,the changes of blood urea nitrogen(BUN),creatinine(Crea),alanine transaminase(ALT),aspartate transaminase(AST)in serum were evaluated by biochemical analysis,blood samples were collected via retro-orbital route under anesthesia and cytokines(TNF-?,IL-6 and IL-1?)were examined by mouse ELISA kits.The pathological changes of kidneys tissues were observed with HE staining.The expression of p-I?B-a and NF-?B/P65 protein were detected by Western blot.Results:1.HE staining results showed that:In stark contrast to control group,LPS-induced histopathological changes in renal tissues were observed obviously,for instance the edema of renal tubular epithelial cells and glomerular atrophy,the dilation of renal capsule cavity,destruction of tubular structures,the epithelial cells of local focal necrosis collapse,and renal interstitial edema of epithelial cells.The pretreatment of with IAC(50,100,200mL/kg)significantly attenuated LPS-induced epithelial atrophy and necrosis and interstitial edema by various degrees.2.The renal weight index of each group:It was found that compared with the control group,LPS group was significantly higher.However,renal weight index in IAC group and DEX group were significantly lower than that of LPS group.3.The concentrations of Crea and BUN:The BUN and Crea levels in LPS group mice were higher than that of control group.BUN and Crea levels in IAC group and Dex group were lower than that of LPS group.4.The concentrations of ALT and AST:The ALT and AST levels in LPS group mice were higher than that of control group.The ALT and AST levels in IAC group and Dex group were lower than that of LPS group*5.The levels of serum TNF-a and IL-1?:LPS group was higher than that of control group.However,compared with the LPS group,TNF-? and IL-1?levels in IAC group and DEX group were significantly reduced.6.The expressions of renal tissue p-I?B-a and Nuclear NF-?B/P65 protein:The p-I?B-a and nuclear NF-?B/P65 protein expression levels in LPS group were significantly higher than that of control group.However,compared with the LPS group,p-I?B-a and nuclear NF-?B/P65 expression levels in IAC group and Dex group were significantly reduced.Conclusion:1.This study showed that Isoacteoside could ameliorate the renal function,inhibit the level of inflammatory factors such as TNF-?,IL-1?,reduce renal pathological damage,and protect the kidney against acute injury induced by sepsis.2.Isoacteoside can inhibit inflammation in septic mice and protect the kidney injury induced by sepsis though NF-?B signaling pathway.