【摘要】 目的:探讨吡咯烷二硫代氨基甲酸酯(PDTC)的降糖作用及对糖尿病大鼠心肌的保护作用。方法:37只雄性Wistar大鼠,随机分为正常对照组(NC)和高脂饮食组(HFD)。喂养8周后,高脂饮食组大鼠腹腔注射单剂量链脲佐菌素(STZ)27 mg/kg复制2型糖尿病大鼠模型。造模成功后再随机分为模型组和PDTC治疗组。PDTC治疗组大鼠每天腹腔注射PDTC(50 mg/kg)1次,模型组和正常对照组每天注射相同剂量的生理盐水,连续注射1周后,检测血糖及各种生化指标,处死大鼠。检测心肌组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性;用透射电镜观察心肌组织的超微结构;用免疫组化观察心肌组织中诱导型一氧化氮合酶(iNOS)和硝基酪氨酸(NT)的表达。结果:糖尿病模型组与正常对照组大鼠相比,血糖和MDA水平显著升高,SOD和GSH-Px活性明显下降(P<0.01);PDTC治疗后,血糖和MDA水平明显降低,SOD和GSH-Px活性明显升高(P<0.01)。糖尿病组心肌变性坏死、线粒体损伤及炎症细胞浸润;PDTC治疗后线粒体损伤明显减轻。糖尿病组较正常对照组心肌中iNOS和NT的表达均明显增加;PDTC治疗后iNOS和NT的表达均明显减少。结论:高血糖可引起氧化应激,使心肌组织中iNOS和NT生成过多,损伤了心肌细胞的结构和功能。PDTC不仅具有降糖作用,而且还可以通过减少iNOS和NT的产生,进而阻止或延缓糖尿病心肌病的发生。更多还原

【Abstract】 AIM:To investigate the effect of pyrrolidine dithiocarbamate(PDTC) on reducing blood glucose level and its protective effect on cardiac muscles in diabetic rats.METHODS: Thirty-seven male Wistar rats were randomly divided into normal control(NC) group and the high-fat diet(HFD) group.After 8 weeks of feeding,the rats in high-fat diet group were given a single dose of streptozotocin(STZ,27 mg/kg) by intraperitoneal injection to induce type 2 diabetes.The diabetic rats were randomly divided into diabetes mellitus(DM) group and PDTC treatment(PDTC) group.The rats in PDTC group were intraperitoneally injected with PDTC(50 mg/kg) once daily.The rats in NC group and DM group were injected with equivalent volume of saline in the same way.After 1-week treatment,the level of blood glucose was measured,and all animals were killed.The concentration of malondialdehyde(MDA) and the activity of superoxide dismutases(SOD) and glutathione peroxidase(GSHPx) were determined using commercial kits.The ultrastructural changes of the cardiac tissues were observed under transmission electron microscope.The expression of inducible nitric oxide synthase(iNOS) and content of nitrotyrosine was examined by the method of immunohistochemistry.RESULTS: The levels of blood glucose and MDA were significantly higher,while the activity of SOD and GSH-Px was lower in DM group than those in NC group(P<0.01).Treatment with PDTC markedly decreased the blood glucose and MDA content,and increased the activity of SOD and GSH-Px.Severe degeneration,necrosis,mitochondrial damage and inflammatory cell infiltration were found in the cardiac tissues in DM group.Treatment with PDTC markedly attenuated mitochondrial damage.The expression of iNOS and content of nitrotyrosine in cardiac tissues were significantly higher in DM group than those in NC group,and those were reduced after administration of PDTC.CONCLUSION: High glucose induces oxidative stress,increases the expression of iNOS and content of nitrotyrosine,and impairs the structure and function of myocardium.PDTC reduces blood glucose level,decreases the expression of iNOS and content of nitrotyrosine,and delays or attenuates the development of diabetic cardiomyopathy in diabetic rats.更多还原