| ObjectiveAsymmetric dimethylarginine (ADMA) in which leading to arteriosclerosis andhypertension and so on endothelial dysfunction(ED) is an endogenous nitric oxide(NO) inhibitor recognized as an independent risk factor for endothelial dysfunctionand coronary heart diseases. The purpose of this study is1)to establish Diabetic ratsby using high fatty and high saccharide forage to fed and low dose of streptozotocin（STZ）to ntraperitoneal inject;2)to observe the change of level of ADMA andendothelial function in Diabetic rats;3) to observe the change of level of ADMAand endothelial function by using rosuvastatain and investigate the possiblemechanisms.Methods1.construction of animal model8-week-old SPF male SD rats,30were randomly selected out of eight normaldiet, served as normal controls. The remaining22rats were fed with10%white sugar,12%lard,2%cholesterol,0.5%bile salts in fat, high sugar feed.22SD male rats werefed with high fatty and high saccharide forage，then were ntraperitoneal injected withlow dose of streptozotocin（STZ）only once to evoke experimental type2diabetic rats。Two months later, the use of high-fat, high-sugar diet for rats30mg/kg oflow-dose streptozotocin, a single intraperitoneal injection of normal controlrats usingthe same dose of citric acid-sodium citrate sodium buffer, a single intraperitonealinjection, one week after test the tail vein blood blood glucose levels, blood sugar ishigher than16.7mmol/L, as a standard screening experimental type2diabetesmice,total into a mold16.The modeling rats were randomly divided in to diabetes groupand rosuvastatin group.2.Intervention of drugsThe normal group fed a normal diet, the diabetic group and the rosuvastatingroup fed high-fat, high sugar diet, the groups were kept in SPF grade environment,daily replacement of bedding and water.Into a mold within one week after repeatedchecks of blood sugar, until the blood sugar stable,Rosuvastatain group were takenRosuvastatain by intragastric administration.After group were interfered in for8weeks, blood low density lipoprotein cholesterol(LDL-C)，triglyceride(TG)，serumtotal cholesterol(TC)and ADMA were measured, the appearance of vascularendothelial cell was observed with transmission electron microscope (TEM).Results1. Diabetic rats assessmentsHigh-sugar high-fat diet for8weeks after20intraperitoneal injection of STZrats typical "polyphagia, polydipsia, polyuria, weight loss," a little more than changetheir blood glucose levels higher than the diabetes diagnostic criteria:16.7mmol/L,16modeling success rate of about72%. Diabetic group and the rosuvastatin group exception: compared with normal group, TC (2.73±0.119,2.178±0.116mmol/L,the VS1.945±0.255mmol/L,), TG (1.951±0.104,1.611±0.301mmol/L, VS1.472±0.216mmol/L), LDL (1.762±0.984,1.268±0.105mmol/L VS0.499±0.152mmol/L) were significantly higher (P <0.05); HDL (0.57±0.135,0.834±0.008mmol/L, VS1.208±0.166) were significantly decreased (P>0.05).2. Biochemical Changes in blood2.1Changes in blood sugar:The experimental intervention in the diabetic group after8weeks androsuvastatin group blood glucose rise: in the diabetic group (25.84±4.47mmol/L),rosuvastatin group (24.47±4.13mmol/L) than in normal group(6.09±0.46mmol/L) was significantly increased (P <0.05). Comparison between diabetic group androsuvastatin group difference (P>0.05).2.2Dyslipidemia:the experimental intervention8weeks rosuvastatin group rats compared withdiabetic group was significantly lower than the diabetic rats compared to LDL (1.268±0.105the VS1.951±0.104), TG (1.611±.301the VS1.762±0.984), the TC(2.178±0.116the VS2.73±0.119) were significantly lower (P <0.05); and HDL(0.834±0.008, the VS0.57±0.135), there was significantly higher (P <0.05).2.3ADMA:8weeks after the intervention of the experimental diabetes group ADMA levels(608.903±12.853μmol/L) was significantly higher (416.553±9.334μmol/L)(P<0.05); Rosuvastatin group (514.101±21.03μmol/L) compared with the diabetic group were significantly lower (P <0.05).Comparison of results of electron microscopyCompared with normal group, diabetic rats by transmission electron microscopyshowed endothelial cell swelling, necrosis, loss and other traumatic change.Endothelial cells was significantly improved after rosuvastatin intervention underTEM transmission electron microscopy.Conclusions:1. Low-dose streptozotocin streptozotocin normal SD rats can be caused by theformation of type2diabetes model rats high sugar high fat diet for2weeks.2. the model obvious glucose metabolism, lipid metabolism disorders, the ADMAlevels were significantly higher vascular endothelial cell necrosis, loss, damage oftheir endothelial function.3. Rosuvastatin can improve lipid metabolism disorder, ADMA levels weresignificantly lower vascular endothelial cell morphology, function improved, andthis feature is independent of glucose lowering, but not yet independent of thelipid mechanisms, possibly by rosuvastatin reduces LDL ADMA levels reduceand improve endothelial function, there may be synergies between the two. |
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