Treatment Effect Of Insulin On Rats With Acute Kidney Injury Induced By Lipopolysaccharide

Objective:To observe the effects of exogenous Insulin on the serum、urine neutrophil gelatinase associated lipocalin (NGAL) and matrix matallo proteinases-9(MMP-9),and on the renal tissue expression of NGAL and MMP-9in lipopolysaccharide(LPS)-induced acute kidney injury (AKI) in rats,Make clear if insulin can treat LPS-induced AKI and explore its possible protective mechanisms.Methods:LPS-induced AKI model was made by LPS4mg/kg through tail vein injection.72healthy male SD rats of clean grade were randomly divided into nine groups:normal control group,model groups (2h、6h、12h and24h group, respectively), treatment groups (2h、6h、12h and24h group, respectively).Before LPS injection,middle-acting insulin4U/kg was taken through intraperitoneal injection2h ago,normal control group and model groups was taken the same volumn of nomal saline at the same time.After the prescribed time, the rats were killed,the blood、urine and the renal tissue were obtained.Then determined and calculated the serum NGAL、MMP-9、Cpeptide、creatinine (Cr) and blood glucose, urine NGAL/Cr、MMP-9/Cr and (32-microglobulin (β2-MG)/Cr.The sample was made histological obversation under the light microscopy after HE staning,other for examining the expression of NGAL and MMP-9protein by histochemical staining,partly for examining Tumor necrosis factor-a(TNF-a)of the kidney homogenates.Results:①At2h、6h、12h and24h, the levels of serum、urine and renal tissue NGAL were all significantly higher than normal control groups (P<0.01), among them, at2h and6h it increased more significantly; There was high positive correlation between the level of urine NGAL/Cr and extent of Pathological damage (r=0.949, P<0.01)、 between the level of urine NGAL/Cr and expression of renal tissue NGAL (r=0.946, P<0.01).②In model groups, at6h、12h and 24h the levels of serum、urine and renal tissue MMP-9were significantly higher than normal control group(P<0.01), among them, at6h and12h it increased more significantly;There was high positive correlation between expression of renal tissue MMP-9and extent of Pathological damage(r=0.852, P<0.01).③The level of serum creatinine was no significant difference between model groups and normal control group,or between normal control group and treatment groups; In model groups, at12h and24h urine β2-MG/Cr was higher than normal control group(0.01<P<0.05, P<0.01, respectively), In treatment groups, at24h the level of urine (32-MG/Cr was lower than model groups significantly(0.01<P<0.05).④In treatment groups, at2h、6h、12h and24h the levels of serum、 urine and renal tissue NGAL and MMP-9were lower·than model groups,among them treatment groups at12h and24h decrease more significantly(P<0.05),and the level of NGAL decrease more significantly than MMP-9.⑤In model groups including2h、6h、12h and24h groups the level of TNF-a from the kidney homogenates were significantly higher than normal control groups(P<0.01),among them model group at6h increased more significantly;every treatment group was lower than model groups,among them6h and12h groups decrease more significantly.⑥Every model group the level of blood glucose were higher than normal control group,among them6h and12h groups increaseed more significantly(P<0.01); every treatment group the level of blood glucose were lower than model groups,among them6h and12h groups decrease more significantly(0.01<P<0.05).⑦Every model group the level of serum C-peptide were significantly higher than normal control group(P<0.01), among them2h and6h groups increased more significantly;In treatment groups, at6h、12h and24h the level of serum C-peptide were lower than LPS groups,among them12and24h groups decrease more significantly(P<0.01).⑧There was positive correlation between the level of serum NGAL and C-peptide (r=0.797,0.01<P<0.05), the level of serum NGAL and blood glucose (r=0.695,0.01＜P <0.05), the level of serum NGAL and TNF-a from the kidney homogenates (r=0.853,0.01<P<0.05)Conclusions:①LPS may induce kidney injury by up-regulating the expression of NGAL> MMP-9、TNF-a or inducing high blood glucose and insulin resistance.②Serum、urine and kidney NGAL all increase significantly in AKI,among them,There was high positive correlation between the level of urine NGAL/Cr and extent of Pathological damage.It suggested that determing urine NGAL can help to diagnose、estimate the extent of kidney injury and estimate the development about AKI.③Insulin can treat LPS-induced AKI by down-regulating NGAL and MMP-9、reducing insulin resistance and decreasing blood glucose.