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Lipoic Acid Reduces Oxidative Stress In Diabetic Rats And The Protective Effect On Kidney

Posted on:2012-01-17Degree:MasterType:Thesis
Country:ChinaCandidate:X H DaiFull Text:PDF
GTID:2154330332996065Subject:Endocrinology
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Background and objective:In the 21st century, diabetes mellitus (DM) has become one of the highest morbidity and mortality of chronic diseases, but its precise mechanism has not been completely cleared. With further research of free radical oxidative damage in recent years, Oxidative stress and the development of diabetes and its complications are closely related,that is the same injury in the pathogenesis of the common basis of high glucose-oxidative stress. Diabetes mellitus with oxidative stress injury,causing diabetic complications has been widely confirmed, therefore, in the treatment of diabetes and its complications, antioxidant therapy is a current concern.Diabetic nephropathy is one of the major microvascular disease,what is end-stage renal disease for the first reason,and lacks effective treatment currently,its occurrence is also closely related with oxidative stress.so finding effective drugs against oxidative damage in order to reduce diabetes renal cell damage and delay the deterioration of renal function to become the treatment of diabetic nephropathy in a new direction.This study aims to observe antioxidants lipoic acid (LA) on oxidatie stress level of diabetic rats and its protective effect on diabetic kidney in rats.Method:Intraperitoneal injection of streptozotocin (STZ) induced diabetic rats, diabetic rats were randomly divided into diabetes group (DM group) and intervention of a-lipoic acid group (LA group), normal rats group (NC group). After 8 weeks, weighed, measured blood serum MDA, blood glucose,24-hour urine albumin.Isolated kidneys, weighed the left kidney weight, sliced renal tissue and stained HE, renal tissue nuclear factor-kappa B (NF-KB), tumor necrosis factor-a (TNF-α), IL-1β(IL-1β)expressed by immunohistochemistry.Results:(1)Compared with NC group, DM group and the LA group after 8 weeks blood serum MDA, blood glucose was significantly higher(P<0.05), Compared with DM group, LA group serum MDA is decreased(P<0.05),The blood sugar is low,but no statistical significance(P>0.05).(2)Compared with NC group,DM group and the LA group body weight decreased significantly(P<0.05),kidney weight,kidney fat index(KW/BW),urinary albumin was significantly higher (P<0.05),Compared with DM group,LA group kidney fat index,urinary albumin decreased (P<0.05), kidney weight reduced weight gained, but no statistical significance (P>0.05).(3) NF-KB brown particles were distributed in the nucleus, TNF-α, IL-1βbrown particles were distributed in the cytoplasm,positive cells are mainly in the glomerular endothelial cells, epithelial cells, mesangial cells, NC group renal tissue NF-KB, TNF-β, IL-1βexpression were weak. compared with the NC group,DM group and the LA group renal tissue NF-KB, TNF-α, IL-1βthe average gray reduced(P<0.05);LA group compared with DM group renal tissue NF-KB, TNF-α, IL-1βthe average gray increased(P<0.05).(4)NC group of glomerular volume,mesangial extracellular matrix and cell distribution is normal, no renal interstitial infiltration of inflammatory cells, DM group glomerular hypertrophy,mesangial cell Proliferation,extracellular matrix accumulation were increased, LA group The morphological abnormalities improved significantly.(5) the levels of urinary albumin was positively correlated with serum MDA(r=0.584, p<0.01), and negatively correlated with renal expression of NF-KB(r=-0.667, p<0.01);the serum MDA was negatively correlated with renal expression of NF-KB(r=-0.589, p<0.01);the renal tissue expression of NF-KB was positively correlated with TNF-α, IL-1β(r= 0.795,p<0.01; r= 0.701, p<0.01);at the 0.05 level (bilateral) is related, at the 0.01 level (bilateral) is significantly related.Conclusion:There exists oxidative stress in diabetic rats. High blood glucose causes glomerular NF-KB, TNF-α, IL-1βexpression increased.lipoic acid may be reduce the renal pathological injury by reducing the level of oxidative stress in diabetic rats, reduceing NF-KB, TNF-α, IL-1βexpression, reducing the urinary albumin and play a role in renal protection.
Keywords/Search Tags:lipoic acid, diabetes mellitus, oxidative stress, NF-κB, TNF-α, IL-1β
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