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The Effects Of Lipoic Acid On The Expressions Of Oxidative Stress Levels And Of NF-KB And ICAM-1 And VCAM-1 In Diabetic Rats Kidneys

Posted on:2012-07-11Degree:MasterType:Thesis
Country:ChinaCandidate:W P WangFull Text:PDF
GTID:2154330332496070Subject:Endocrine
Abstract/Summary:PDF Full Text Request
Objective:This study was based on the models of diabetic rats by single intrapertioneal injection of streptozocin(STZ) and the diabetic rat models were intervened with the medicine of lipoic-acid,in order to observe the changes of hypertrophy index of rat kidney,blood glucose, MDA,24 hours microalbuminuria and the expression of nuclear factor-kappaB (NF-KB), intercellular adhesion molecule-1 (ICAM-1),vascular cell adhesion molecule-1 (VCAM-1)in diabetic rat kidneys.The purpose of his study is to further probe into the protection mechanism of lipoic-acid for the diabetic rat kidney.Method:Thirty male Wister rats of eight weeks were randomly divided into three groups: normal control group(group A),diabetes mellitus model group(group B), lipoic-acid treatment group (group C). There were 10 rats for each group.After the rats were raised for a week to adapt the surroundings,the rats of group B and group C were made diabetic rat models by enterocoelia injection of streptozoein at a dose of 60mg/kg.Rats of group A were received the same dose of buffer solution instead of STZ .Three days later,the rats whose blood glucose higher or equal to 16.7mmol/l were diabetic rats.The group C were given lipoic-acid(60mg/kg/d) for 8 weeks,at the same time, the other two groups were intraperited with the same dose physiological saline.At the end of the 8thweek, the results were measured, including of the weight of kidney, blood glucose,MDA,24h microalbuminuria and the expression on NF-KB and ICAM-1 and VCAM-1 in the diabetic rat kidneys.Results:(1)The common indexs of the ratsAfter the rats were treated for 8 weeks with lipoic acid, the weights of group B and group C rats were significantly decreased than group A(P<0.05),however there was not significant difference either group B or group C in the weights of diabetic rats(P>0.05).After the rats were treated for 8 weeks, The blood glucoses of group B and group C rats were significant higher than group A (P<0.05),there were no significant difference either in group B or in group C (P>0.05).(2)The changes of MDA and 24 hours microalbuminuriaThe MDA levels both in group B and in group C rats were significantly higher than the group A (P<0.05);however MDA in group C were significantly lower than group B(P<0.05); In comparison with group A rats, 24 hours microalbuminuria flushing both in group B and in group C were significantly increased (P<0.05), 24 hours microalbuminuria flushing in group C was lower than the group B after they were treated for 8weeks(P<0.05).(3) The rat kidney weight and hypertrophy index of the rat kidneyAfter the diabetic rats were treated with lipoic acid for 8 weeks, the weights of the kidneys both in groups B and in group C were higher than group A(,P<0.05),nevertheless there was no significant difference neither in group B or in group C(P>0.05); Hypertrophy index of kidney both in group B and in group C rats were higher than group A(P<0.05),compared with group B, the hypertrophy index in group C rats were significant lower(P<0.05).(4) The expressions on NF-KB and ICAM-1and VCAM-1 in the rat kidney by the method of immunohistochemistryIn this study,the grey value was regard as an index to assess the positive expression on NF-KB and ICAM-1 and VCAM-1 in the rat glomerular , the relationship between the grey value and the positive expression was adverse,the lower grey value,the stronger the positive expression.In this lab , the positive expression on NF-KB in normal group were rarely ,however the positive expression on NF-KB in diabetic group were significantly strong(P<0.05),which showed that the cell nucleus of glomerlar epithelial cell and endotheliocyte of rat became buffy . After the diabetic rats were treated with lipoic acid for 8 weeks, the positive expression of group C on NF-KB were decreased(P<0.05).The results of the group B and the group C on ICAM-1 and VCAM-1 showed that the positive expression in normal group were rarely,that the positive expression on ICAM-1 and VCAM-1 in diabetic group were significantly strong(P<0.05),and the cytolymph of glomerlar of rat became buffy . After the diabetic rats were treated with lipoic acid for 8 weeks, the positive expression on ICAM-1 and VCAM-1 of group C were decreased(P<0.05).(5) The correlation analysisIn this study ,24h microalbuminuria flushing of the diabetic rats was positively correlated with MDA(r=0.584,P<0.01),however 24h microalbuminuria were negatively correlated with the gray value of NF-KB and ICAM-1 and VCAM-1(NF-KB:r=-0.667, ICAM-1:r=-0.551 ,VCAM-1:r=-0.586)( P<0.01) ; The gray value of NF-KB were positively correlated with both ICAM-1and VCAM-1(ICAM-1:r=-0.831,VCAM-1:r=0.771)(P<0.01),the gray value of NF-KB in diabetic rats were negatively correlated with MDA(r=0.589,P<0.01).Conclusion:(1) The oxidative stress levels in vivo of diabetic rats were increased ,which might injury the kidney by many ways.(2) For diabetic rats, 24 hour microalbuminuria of flushing were increased and the expressions on NF-KB , ICAM-1,VCAM-1 in diabetic rats glomerulars were significantly increased.(3) Lipoic acid could decrease microalbuminuria of flushing of diabetic rats and protect the rat kidney. One of the mechanisms on the protecting role of lipoic acid were that lipoic acid can decrease the oxidative stress levels of diabetic rats, and controlled the expression of NF-KB,ICAM-1, VCAM-1 in diabetic rat kidney ,and decrease the inflammation in diabetic rat kidney.
Keywords/Search Tags:diabetes, oxidative stress, ICAM-1, VCAM-1, lipoic acid
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