Effects Of Oxidative Stress On The Transformation Of Diabetic Mice And Its Great Vascular Complication

Background Accounted for the vast majority of the diabetic group, the incidence rate of type2diabetes mellitus (T2DM) is increasing every year, and its vascular complications are the main factors of morbidity and mortality rate in patients with DM. Growing number of studies have shown oxidative stress is one of the pathophysiological mechanisms in DM.Objective To establish the diabetic mice model and to investigate the effects of oxidative stress on the progress of diabetes, the change of redox state.the effect of vascular complications and the activity of glycometabolism-enzyme after anti-oxidant. investigate the effect of antioxidant on the relative of vascular complications and to provide fully theoretical proof of antioxidant applied in clinical treatment.Methods1Sixty healthy specific-pathogen free male KM mice aged four weeks were housed in an environmentally controlled room and after accustomed for one week, mice were randomly divided into two groups:the normal control group(n=10) and the high-fat and glouce model group(n=70).2Then these mice of the the high-fat and glouce model group were injected a low dose streptozotocin (150mg/kg) after3weeks by intraperitoneal injection in order to transform into diabetic mice, while the normal group were injected equal quantity citric acid buffer. Then the early-diabetic model group was established by testing FBG (10-11mmol/L) for three days(five mice were not conformed). These mice were randomly divided into four groups:diabetic model group (DM, n=10), alpha-lipoic acid (LA, n=10) group, oxidative stress group (OS. n=10) and anti-oxidative stress group (AO, n=35). The AO group were feed by ferrous sulfate dieat and randomly divided into seven group:the control group, alpha-lipoic acid group (LA group, n=5), corosolic acid group (CA group, n=5), grape seed proanthocyanidins group (GSPE group, n=5), quercetin group (QC group, n=5) and tea polyphenols (TP group, n=5).3At end of the sixth week with antioxidant. The ratio of GSH and GSSG, the inhibition ratio of SOD and FINS were measured from these blood preparations.4The abdominal aorta and part of pancreas tissue of diabetes group, alpha-lipoic acid group and normal group which were gotten and determined the change of the endotheliocyte and muscular layer of abdominal aorta and pancreatic island with electron microscopy:observed the change of pancreatic island with hematoxylin and eosin stain. Determined the activity of pyruvate carboxylase and hexokinase correlated glycometabolism with ultraviolet spectropHotometer.Results1The weight of the high-fat and glouce diet group was significantly higher than that of the normal control group after six weeks (P<0.05).2The weight of AO group after treated with antioxidant for two weeks was significantly lower than that of the normal control group (P<0.05); TP group was espically obvious (P<0.05).3The DM group were fed with high-fat and glouce diet continuatively. the OS group altered high-fat and glouce contained5%ferrous sulfate after injected a low dose of streptozotocin (150mg/kg) with intraperitoneal injection. These mice were all transformed into diabetic mice at the fifth week (P<0.05).4After treated with alpha-lipoic acid for two weeks, the FBG of the LA group was significantly lower than that of the NC group (P<0.05).5The levels of FBG and SBG of the alpha-lipoic acid group after treated with alpha-lipoic acid for six weeks was significantly lower than that of the diabetic model group (P<0.05). The levels of FBG, FINS and SBG of the DM group was significantly higher than that of the normal control group (P<0.05).6The level of SODI, GSH/GSSG and the Lee’ index of the diabetic model group was significantly higher than that of the normal control group (P<0.05), while the level of GSH/GSSG and the Lee’ index of the alpha-lipoic acid group was significantly higher than that of the normal control group (P<0.05); the activity of PC and HK of the LA group was significantly lower than that of the diabetic model group (P<0.05), while the DM group was significantly higher than that of the NC group (P<0.05).7Light microscopy shows (hematoxylin and eosin stain):the pancreatic tissue and the volume of isletcells were normal. The volume of isletcells arranged disorderly shrinked, and the cellnucleus arranged closely in the diabetic model group. The isletcells renewed a little.8The ultrastructure of isletcells showed by electric mirror:the mitochondria of isletcells was normal, the mitochondrial cristae arranged orderly, the rough surfaced endoplasmic reticulum was affluentcontrol. the golgi apparatus and the exocrine glands was normal in the normal control group. The mitochondria of isletcells appeared autophagy. the mitochondrial cristae reduced or disappeared, the rough surfaced endoplasmic reticulum and the golgi apparatus appeared dilatation in the diabetic model group. The number of the mitochondria in the alpha-lipoic acid group increased indicated it renewed a little.9The ultrastructure of aorta endothelium in the diabetic model group showed pathologic changes while the the alpha-lipoic acid group was between in the diabetic model group and the normal control group at the end of experiment.Conclusions1Oxidative stress parcipated in the progresses of the diabetes.2After treated six antioxidants from the beginning to the end, anti-oxidant can prevent diabetes.the TP group was especially obvious.3So the alpha-lipoic acid can early obviously improve and provent the occurrence diabetic macroangiopathy.