| Objective:Our study was subjected to observe the effects ofα-lipoic acid on the metabolism of lipid and glucose and the level of oxidative stress in the streptozotocin induced diabetic Wistar rat, and further explore its mechanism.Methods:Fifty healthy male Wistar rats(weighing 180-200g) were randomly divided into two groups after adaptive feeding with ordinary food for 7 days, the normal control group(NC n=8) and the experimental group (EG n=42). The rats of NC group were continued to feed with primary diet while the rats of experimental group were switched to high fat diet, then at the end of the 4th weeks those rats of EG were gived STZ (30mg/kg) intraperitoneal injection singly after overnight fasting 12 hours which was dissolved in 0.1mol/L citric acid-citrate sodium buffer (pH4.2), and the NC were injected with the same amount of citric acid-citrate sodium buffer only. The tail vein blood glucose≥16.7mmol/L after 72hs was consided to be diabetic rat and taken into the experiment. All of the diabetic rats was feed with high-fat diet for another 4 weeks, after that they were randomly divided into four groups, the low-dose group ofα-lipoic acid (LLA,α-lipoic acid 30mg/kg.d, n=8), the middle-dose group (MLA,α-lipoic acid 60mg/kg.d, n=8), the high-dose group (HLA,α-lipoic acid 120mg/kg.d, n=8), and the diabetic control group (DC, Sodium Chloride 2ml/d,n=8). During the experiment, animals eat and drink ad libitum, Body weight and blood glcose were measured once a week. After 4 weeks'drug intervention all the rats were anesthetized by pentobarbital sodium after overnight fasting for 12 hours, blood was taken from superior vena cava for the testing of blood lipids profile, glucose, glycated hemoglobin and so on. Liver tissue was taken immediately and put into the EP tubes and then frozened in the liquid nitrogen. After the experiment all the tissue was stored in-80℃refrigerator. Western blot method was used to detect the protein expression level of AMPKa and phosphorylated AMPK (ph-AMPK), colorimetric assay was used to measure the level of MDA and T-AOC.Result:The levels of glucose, Triglyceride, cholesterol, low density lipoprotein and glycosylated hemoglobin in the DC group were significantly higher than those of NC group, however the level of high density lipoprotein is decreased obviously(P> 0.05), while a-lipoic acid intervention can decrese the levels of Triglyceride, cholesterol, low density lipoprotein and glycosylated hemoglobin and increse the level of high density lipoprotein, and the blood glucose levels of the HLA and MLA group were all decreased(P>0.05). Meanwhile, the level of MDA was higher in the DC group compared with NC, but the expression of AMPKa, phosphorylated AMPK and the level of T-AOC were decreased(P>0.05). A-lipoic acid intervention can reduce the level of MDA and enchance the the expression of AMPKa and phosphorylated AMPKa and increase the level of T-AOC in a dose-dependent manner.Conclusion:This study further confirmed that the level of blood glucose, TG, TC, LDL, HbAlc in the diabetic rats were significantly higher than those of normal controls, while HDL levels was significantly decreased. Long-lasting high level of blood sugar and lipid profile may lead to the disorder of energy metabolism and generate more oxyradical, and result in the excesive oxidative stress, which could promote the development of diabetic complications. Alpha-lipoic acid can significantly increase the activity of AMPKa and ph-AMPKa in the liver, decrease the level of MDA, which showed an protective effect of improving "glycolipid toxic" and reduce the level of oxidative stress in diabetes.
|
PDF Full Text Request