贵阳代谢记忆分析.pptVIP

尽早控制 尽快达标 持久稳定 目前对血糖控制的观念 * * * 细胞内高血糖诱导线粒体过量产生超氧化物，这是糖尿病并发症发病机制的第一步也是最重要的一步，随后激活多元醇通路和氨基己糖通路，AGEs形成增多，蛋白激酶C和NF-γB的激活。在高血糖环境中线粒体蛋白糖基化，诱导线粒体产生过量超负氧离子。在这种情况下，即使高血糖得到纠正，糖化的线粒体继续产生过量超负氧离子，活化上述与糖尿病并发症发生有关的通路。 * Studies have shown that good metabolic control (GC) is beneficial in slowing the progression of nephropathy in diabetes, and if the duration of poor metabolic control (PC) is prolonged before reinstitution of GC, nephropathy is not easily reversed. This study is to identify the biochemical abnormalities that could contribute to the resistance of nephropathy to reverse after establishment of GC in rats. The effect of reinstitution of GC and its duration is evaluated on oxidative stress and nitric oxide (NO) levels in the renal cortex and urine of diabetic rats. The rats were maintained in GC (5% glycated hemoglobin, GHb) soon after or 6 months after induction of hyperglycemia, and were sacrificed 13 months after induction of diabetes. For rats in which GC was initiated soon after induction of diabetes, oxidative stress [as measured by the levels of lipid peroxides (LPOs), 8-hydroxy-2V-deoxyguanosine (8-OHdG), and reduced glutathione (GSH)] and NO in urine and renal cortex were not different from that observed in normal control rats, but when reinstitution of GC was delayed for 6 months after induction of diabetes, oxidative stress and NO remain elevated in both urine and renal cortex. This suggests that hyperglycemia-induced oxidative stress and NO can be prevented if GC is initiated very early, but are not easily reversed if PC is maintained for longer durations.Understanding the mechanisms responsible for this phenomenon could reveal novel means to reverse nephropathy in diabetic patients. * 氧化应激的脂质过氧化产物上升：8-羟基-脱氧鸟苷，PC-GC组24小时尿8-OHdG比正常组高50％，但是无统计学差异。 * 过氧化物酶： * 体内抗氧化系统的物质浓度的下降：谷胱甘肽过氧化物酶。PC-GC组比正常组低，但是无统计学差异。 * * * * 体内抗氧化系统的物质浓度的下降：超氧化物歧化酶 * AGEs与细胞外基质和基底膜的分子相互交联， 交联后AGE蛋白溶解度降低，从而影响结缔组织和细胞外基质的功能，基底膜增厚。 AGEs通过与其受体[晚期糖基化终产物受体(RAGE)]结合，影响糖尿病大血管和微血管并发症的发生。