Background Diabetic cardiovascular complication is a major cause of mortality in type 2 diabetic patients.Hyperglycemia markedly increases the risk of cardiovascular disease.Endothelial dysfunction is common in type 2...Background Diabetic cardiovascular complication is a major cause of mortality in type 2 diabetic patients.Hyperglycemia markedly increases the risk of cardiovascular disease.Endothelial dysfunction is common in type 2 diabetes mellitus (DM) and is an early indicator of diabetic vascular disease.Therefore,it is necessary to identify the effect of different hypoglycemic agents on vascular endothelium.The aim of the study was to examine and compare the effects of metformin and gliquidone on atherosclerotic lesions in streptozotocin-induced diabetic rats.Methods Forty male Sprague-Dawley rats (age,8 weeks; weight,180-200 g) were included in this study and fed with a normal chow diet for 1 week.Rats (n=10) served as the normal control group (NC group) were fed with a normal chow for another 2 weeks and received an injection of saline.The rest 30 rats fed with a high-fat diet for 2 weeks and injected streptozotocin were randomly assigned to three groups (n=10 rats per group) as follow:type 2 DM group (DM group),DM + gliquidone group (GLI group) and DM + metformin group (MET group).Five weeks later,all rats were fasted overnight and taken tail blood samples for biochemical determinations.Then rats in the NC and DM groups were administrated with normal saline,while rats in the MET and GLI groups were administrated with metformin (100 mg/kg) or gliquidone (10 mg/kg),respectively.All medicines were given via intragastric administration for 8 weeks.After 16 weeks,plasma triglyceride (TG),total cholesterol (TC),low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C) were measured.The aortic arch was isolated from diabetic rats and was assessed by pathological sectioning using H&E staining.Results Metformin treatment prevented weight gain ((315.80±52.16) g vs.(318.70±68.48) g,P=0.773),improved plasma TG,HDL-C and LDL-C levels (P=0.006,0.003,0.001,respectively,all P <0.05).However,gliquidone showed no significant effects on plasma TG and TC levels (P=0.819,0.053,respectively).LDL-C and HDL-C in the GLI group changed ((0.46±0.10) mmol/L vs.(0.36±0.14) mmol/L,P=0.007; (0.99±0.27) mmol/L vs.(1.11±0.18) mmol/L,P=0.049).Both metformin and gliquidone treatment lowered blood glucose levels (P=0.001,0.004,respectively,P <0.05).Under light microscopy,no changes were observed in the aortic wall structure of each layer; the intima was smooth and the membrane elastic fibers were normal in the NC group.In the DM group,the aortic wall structure was unclear,the intima was thickened with irregular intima,and membrane elastic fibers collapsed.The aortic intima in the MET and GLI groups was smoother compared with the DM group,but the endothelial structure of the MET group was closer to that of the NC group.Conclusions Both metformin and gliquidone have anti-atherosclerotic effects.But the endothelial structure of the MET group was closer to that of the NC group.Metformin and gliquidone therapy can reduce serum level of LDL-C and increase level of HDL-C,whereas gliquidone therapy did not lose weight and decrease serum level of TG.These data may have important implications for the treatment of patients with type 2 DM.展开更多
In this study, we reported and validated a novel and sensitive reversed-phase liquid chromatographic method for the simultaneous determination of irbesartan, candesartan, gliquidone and pioglitazone. Separation was pe...In this study, we reported and validated a novel and sensitive reversed-phase liquid chromatographic method for the simultaneous determination of irbesartan, candesartan, gliquidone and pioglitazone. Separation was performed at 230 nm using a mobile phase consisting of methanol–water(90:10, v/v) with a flow rate of 1 mL/min. p H was adjusted to 3.5 with phosphoric acid. The concentration-response relationship was found linear over a concentration range of 5–25 μg/mL for all of the analytes tested. The limits of detection and quantification were 0.83 and 2.78 for irbesartan, 0.30 and 1.01 for candesartan, 1.11 and 3.93 for gliquidone, and 0.41 and 1.41 μg/mL for pioglitazone, respectively. Described method permitted the successful determination of these drugs in human serum. The developed method was simple, rapid, and it did not require extensive sample purification.展开更多
文摘Background Diabetic cardiovascular complication is a major cause of mortality in type 2 diabetic patients.Hyperglycemia markedly increases the risk of cardiovascular disease.Endothelial dysfunction is common in type 2 diabetes mellitus (DM) and is an early indicator of diabetic vascular disease.Therefore,it is necessary to identify the effect of different hypoglycemic agents on vascular endothelium.The aim of the study was to examine and compare the effects of metformin and gliquidone on atherosclerotic lesions in streptozotocin-induced diabetic rats.Methods Forty male Sprague-Dawley rats (age,8 weeks; weight,180-200 g) were included in this study and fed with a normal chow diet for 1 week.Rats (n=10) served as the normal control group (NC group) were fed with a normal chow for another 2 weeks and received an injection of saline.The rest 30 rats fed with a high-fat diet for 2 weeks and injected streptozotocin were randomly assigned to three groups (n=10 rats per group) as follow:type 2 DM group (DM group),DM + gliquidone group (GLI group) and DM + metformin group (MET group).Five weeks later,all rats were fasted overnight and taken tail blood samples for biochemical determinations.Then rats in the NC and DM groups were administrated with normal saline,while rats in the MET and GLI groups were administrated with metformin (100 mg/kg) or gliquidone (10 mg/kg),respectively.All medicines were given via intragastric administration for 8 weeks.After 16 weeks,plasma triglyceride (TG),total cholesterol (TC),low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C) were measured.The aortic arch was isolated from diabetic rats and was assessed by pathological sectioning using H&E staining.Results Metformin treatment prevented weight gain ((315.80±52.16) g vs.(318.70±68.48) g,P=0.773),improved plasma TG,HDL-C and LDL-C levels (P=0.006,0.003,0.001,respectively,all P <0.05).However,gliquidone showed no significant effects on plasma TG and TC levels (P=0.819,0.053,respectively).LDL-C and HDL-C in the GLI group changed ((0.46±0.10) mmol/L vs.(0.36±0.14) mmol/L,P=0.007; (0.99±0.27) mmol/L vs.(1.11±0.18) mmol/L,P=0.049).Both metformin and gliquidone treatment lowered blood glucose levels (P=0.001,0.004,respectively,P <0.05).Under light microscopy,no changes were observed in the aortic wall structure of each layer; the intima was smooth and the membrane elastic fibers were normal in the NC group.In the DM group,the aortic wall structure was unclear,the intima was thickened with irregular intima,and membrane elastic fibers collapsed.The aortic intima in the MET and GLI groups was smoother compared with the DM group,but the endothelial structure of the MET group was closer to that of the NC group.Conclusions Both metformin and gliquidone have anti-atherosclerotic effects.But the endothelial structure of the MET group was closer to that of the NC group.Metformin and gliquidone therapy can reduce serum level of LDL-C and increase level of HDL-C,whereas gliquidone therapy did not lose weight and decrease serum level of TG.These data may have important implications for the treatment of patients with type 2 DM.
文摘In this study, we reported and validated a novel and sensitive reversed-phase liquid chromatographic method for the simultaneous determination of irbesartan, candesartan, gliquidone and pioglitazone. Separation was performed at 230 nm using a mobile phase consisting of methanol–water(90:10, v/v) with a flow rate of 1 mL/min. p H was adjusted to 3.5 with phosphoric acid. The concentration-response relationship was found linear over a concentration range of 5–25 μg/mL for all of the analytes tested. The limits of detection and quantification were 0.83 and 2.78 for irbesartan, 0.30 and 1.01 for candesartan, 1.11 and 3.93 for gliquidone, and 0.41 and 1.41 μg/mL for pioglitazone, respectively. Described method permitted the successful determination of these drugs in human serum. The developed method was simple, rapid, and it did not require extensive sample purification.