Protective Effects Of Astragaloside ? On Early Kidney Damage In Diabetes Mellitus Rats And Its Mechanisms

ObjectivesTo study the effects of astragaloside IV(AS-IV)on early kidney damage and the mechanisms in the diabetes mellitus rats induced by streptozotocin(STZ).MethodsThe model was established with STZ(55 mg·kg-1)by intraperitoneal injection and the model rats were randomly divided into model group,AS-?(20,40,80 mg · kg-1)group.After 8 weeks of administration,body weight,blood glucose,24 hours urinary protein excretion rate(24 h UAER),the level of serum creatinine(Scr),urea nitrogen(BUN),serum SOD,GSH-Px activity and MDA content were measured.HE and PAS staining were used to observe renal histopathology,immunohistochemistry was used to observe the expression of Nrf2?HO-1?NQO1 and Western blot was used to detect the expression of TGF-?1,Nrf2,HO-1,NQO1.Results1.Compared with control group,the body weight decreased significantly and the blood glucose,kidney index increased significantly in model group(p<0.01).Compared with model group,AS-IV(40?80 mg· kg-1)group could decrease blood glucose and kidney index(p<0.05,p<0.01),and AS-IV(80 mg · kg-1)group could increase the body weight(p<0.05).2.Compared with control group,the level of 24 h UAER,BUN and Scr increased significantly in model group(p<0.01).Compared with model group,AS-IV(40?80 mg ·kg-1)group could decrease the level of 24 h UAER,BUN and Scr(p<0.01).3.Compared with control group,MDA content increased significantly and the serum SOD and GSH-Px activity decreased significantly in model group(p<0.01).Compared with model group,AS-IV(40?80 mg·kg-1)group could decrease MDA content(p<0.01),and AS-IV(80 mg · kg-1)group could increase serum SOD and GSH-Px activities(p<0.01).4.HE and PAS staining showed that the glomerular mesangial cells and their matrix were normal.The glomerular mesangial cells proliferated significantly in model group.Compared with model group,the number of extracellular matrix increased,the glomerular capillary basement membrane thickening,PAS positive score was higher(p<0.01).The PAS positive score of AS-IV(40,80 mg · kg-1,)group was decreased significantly(p<0.01).5.Model group significantly increased the expression of Nrf2(p<0.05);AS-IV(40,80 mg·kg-1)group significantly increased the expression of Nrf2,HO-1 and NQO1 protein(p<0.05,p<0.01).6.The expression of TGF-?1 total and nucleus protein of Nrf2 increased significantly in model group(p<0.05).Compared with model group,the expression of TGF-?1 decreased significantly in AS-IV(80 mg ·kg-1)group,expression of total Nrf2,nucleus Nrf2,HO-1 and NQO1 increased significantly in AS-IV(80 mg ·kg-1)group(p<0.05,p<0.01).ConclusionAS-IV can inhibit renal oxidative stress injury.It may be through increasing the serum antioxidant activity and reducing the expression of TGF-?1,activation of Nrf2 pathway,upregulating the expression of antioxidative protein in HO-1 and NQO1.