Objective: To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy. Methods: Targeted Sono VueTM microbubble was prepared b...Objective: To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy. Methods: Targeted Sono VueTM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary micro-bubble Sono Vue by biotin-avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles Sono VueTM or general microbubble Sono Vue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time intensity curve was used to analyse rat kidney perfusion characteristics in different groups. Results: Targeted ultrasound microbubble Sono Vue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles Sono Vue-TM enabled clear development of experimental rat kidney. Time intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased(P<0.05); the peak intensity of medulla increased(P<0.05), and the total area under the curve of medulla increased(P<0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased(P<0.05). The peak intensity of the curve increased(P<0.05), and the total area under the curve increased(P<0.05). Compared with the ordinary angiography group, the peak of GK rat medullacurve in targeted angiography group intensity increased(P<0.05), and the total area under the curve increased(P<0.05). Conclusions: Targeted microbubbles Sono VueTM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.展开更多
Background: This study was conducted to measure the concentration of branched chain amino acid(BCAA) in different species and detect the expression pattern of the liver Bckdha gene in Goto-Kakizaki(GK) rats during typ...Background: This study was conducted to measure the concentration of branched chain amino acid(BCAA) in different species and detect the expression pattern of the liver Bckdha gene in Goto-Kakizaki(GK) rats during type 2 diabetes(T2D)progression.Methods: We measured the concentration of BCAA in GK rats, induced T2D cynomolgus monkeys and T2D humans by liquid chromatography tandem mass spectrometry, and used real-time quantitative PCR to analyze the gene expression of Bckdha and Bckdk, which encode the rate-limiting enzymes in catabolism of,respectively, branched chain amino acids and branched chain α-keto acid dehydrogenase kinase.Results: In this study, we showed that GK rat BCAA concentrations were significantly reduced at 4 and 8 weeks(P < 0.05 and P < 0.01, respectively), while the expression of Bckdha in GK rat liver was increased at 4 and 8 weeks(1.62-fold and1.93-fold, respectively). The BCAA concentrations were significantly reduced in diet-induced T2D cynomolgus monkeys(P < 0.01), but significantly increased in T2D humans(P < 0.001).Conclusions: Our results showed that BCAA concentrations changed at different times and by different amounts in different species and during different periods of T2D progress, and the significant changes of BCAA concentration in the three species indicated that BCAA might participate in the progress of T2D. The results suggested that the increased expression of Bckdha in GK rat liver might partially explain the reduced plasma BCAA concentration at 4 and 8 weeks. Further studies are required to investigate the exact mechanism of BCAA changes in non-obese T2D.展开更多
The number of diabetic patients has recently been increasing all over the world together with lifestyle changes including sedentary life and high-calorie diet intake, and as a result the increase in these suffering fr...The number of diabetic patients has recently been increasing all over the world together with lifestyle changes including sedentary life and high-calorie diet intake, and as a result the increase in these suffering from diabetes mellitus has become a global issue. Diabetic animal models play a key role in bettering our understanding of the pathophysiology of diabetes and in developing new therapies for the disease. Diabetes is classified into two types, type 1 and type 2, and type 2 diabetes is chiefly caused by a depletion of insulin secretion in the pancreas and insulin resistance in peripheral tissues. The Goto-Kakizaki (GK) rat and the Spontaneously Diabetic Torii (SDT) rat are genetic non-obese type 2 diabetic models, and the both rats are considered to be suitable models for investigating the etiology of the depletion of insulin secretion and impaired glucose tolerance. In this review, we overviewed the outline of pathophysiological features in GK rats and SDT rats, including biological parameters and pharmacological responses.展开更多
基金supported by Shanghai Municipal Commission of Health and Family Health Planning Key Projects(NO.20134023)
文摘Objective: To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy. Methods: Targeted Sono VueTM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary micro-bubble Sono Vue by biotin-avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles Sono VueTM or general microbubble Sono Vue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time intensity curve was used to analyse rat kidney perfusion characteristics in different groups. Results: Targeted ultrasound microbubble Sono Vue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles Sono Vue-TM enabled clear development of experimental rat kidney. Time intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased(P<0.05); the peak intensity of medulla increased(P<0.05), and the total area under the curve of medulla increased(P<0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased(P<0.05). The peak intensity of the curve increased(P<0.05), and the total area under the curve increased(P<0.05). Compared with the ordinary angiography group, the peak of GK rat medullacurve in targeted angiography group intensity increased(P<0.05), and the total area under the curve increased(P<0.05). Conclusions: Targeted microbubbles Sono VueTM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.
基金Science and Technology Program of Guangzhou,China,Grant/Award Number:201508020040,201707010330National Science and Technology Support Program,Grant/Award Number:2014BAI03B00,2015BAI07B0+1 种基金Science and Technology Program of Guangdong province,Grant/Award Number:2014B070706020S&T Development Project of Guangdong Academy of Science,Grant/Award Number2017A070702014
文摘Background: This study was conducted to measure the concentration of branched chain amino acid(BCAA) in different species and detect the expression pattern of the liver Bckdha gene in Goto-Kakizaki(GK) rats during type 2 diabetes(T2D)progression.Methods: We measured the concentration of BCAA in GK rats, induced T2D cynomolgus monkeys and T2D humans by liquid chromatography tandem mass spectrometry, and used real-time quantitative PCR to analyze the gene expression of Bckdha and Bckdk, which encode the rate-limiting enzymes in catabolism of,respectively, branched chain amino acids and branched chain α-keto acid dehydrogenase kinase.Results: In this study, we showed that GK rat BCAA concentrations were significantly reduced at 4 and 8 weeks(P < 0.05 and P < 0.01, respectively), while the expression of Bckdha in GK rat liver was increased at 4 and 8 weeks(1.62-fold and1.93-fold, respectively). The BCAA concentrations were significantly reduced in diet-induced T2D cynomolgus monkeys(P < 0.01), but significantly increased in T2D humans(P < 0.001).Conclusions: Our results showed that BCAA concentrations changed at different times and by different amounts in different species and during different periods of T2D progress, and the significant changes of BCAA concentration in the three species indicated that BCAA might participate in the progress of T2D. The results suggested that the increased expression of Bckdha in GK rat liver might partially explain the reduced plasma BCAA concentration at 4 and 8 weeks. Further studies are required to investigate the exact mechanism of BCAA changes in non-obese T2D.
文摘The number of diabetic patients has recently been increasing all over the world together with lifestyle changes including sedentary life and high-calorie diet intake, and as a result the increase in these suffering from diabetes mellitus has become a global issue. Diabetic animal models play a key role in bettering our understanding of the pathophysiology of diabetes and in developing new therapies for the disease. Diabetes is classified into two types, type 1 and type 2, and type 2 diabetes is chiefly caused by a depletion of insulin secretion in the pancreas and insulin resistance in peripheral tissues. The Goto-Kakizaki (GK) rat and the Spontaneously Diabetic Torii (SDT) rat are genetic non-obese type 2 diabetic models, and the both rats are considered to be suitable models for investigating the etiology of the depletion of insulin secretion and impaired glucose tolerance. In this review, we overviewed the outline of pathophysiological features in GK rats and SDT rats, including biological parameters and pharmacological responses.