Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat
Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat
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DOI：
10.1046/j.1523-1755.2002.00207.x
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发表时间：
2002-03-01
影响因子：
19.6
通讯作者：
Baynes, JW
中科院分区：
文献类型：
--
作者：
Degenhardt, TP;Alderson, NL;Baynes, JW
背景。糖或脂质与蛋白质之间的非酶反应以及高级糖基化和脂氧化终产物 (AGE/ALE) 的形成有助于组织蛋白质随着年龄的增长而发生化学修饰和交联。高血糖期间 AGE/ALE 的加速形成与糖尿病并发症的发生有关。在本研究中，我们研究了 AGE/ALE 抑制剂吡哆胺对链脲佐菌素糖尿病大鼠的胶原化学修饰和交联以及肾病发展的影响。方法。用吡哆胺治疗糖尿病大鼠；使用氨基胍（AGE 抑制剂原型）进行了平行实验。通过测量白蛋白尿和血浆肌酐浓度来评估肾脏疾病的进展。通过酶法测定血浆甘油三酯、胆固醇、乳酸和丙酮酸，并通过HPLC和GC-MS测定皮胶原中的AGE/ALE。结果。吡哆胺显着抑制糖尿病大鼠白蛋白尿、血浆肌酐、高脂血症和血浆乳酸/丙酮酸比值的增加，而对血糖或糖化血红蛋白没有影响。AGE/ALE、荧光和糖尿病七个月后，糖尿病大鼠的皮肤胶原蛋白交联增加了约两倍（25％至50％），导致糖尿病大鼠皮肤胶原蛋白的交联和荧光显着降低，但不影响戊糖素。结论：吡哆胺可抑制糖尿病大鼠的肾病进展，并减少高脂血症和明显的氧化还原失衡。吡哆胺和氨基胍对测量的参数有相似的影响，支持涉及 AGE/ALE 抑制的作用机制。
Background. Nonenzymatic reactions between sugars or lipids and protein and formation of advanced glycation and lipoxidation end products (AGE/ALEs) contribute to the chemical modification and cross-linking of tissue proteins with age. Accelerated formation of AGE/ALEs during hyperglycemia is implicated in the development of diabetic complications. In this study, we examined the effect of the AGE/ALE inhibitor pyridoxamine on chemical modification and cross-linking of collagen and development of renal disease in the streptozotocin-diabetic rat.Methods. Diabetic rats were treated with pyridoxaminc; parallel experiments were conducted with aminoguanidine, the prototype AGE inhibitor. Progression of renal disease was evaluated by measurements of albuminuria and plasma creatinine concentration. Plasma triglycerides, cholesterol, lactate and pyruvate were measured by enzymatic assays, and AGE/ ALEs in skin colla(Yen by HPLC and GC-MS assays.Results. Pyridoxamine significantly inhibited the increase in albuminuria, plasma creatinine, hyperlipidemia and plasma lactate/pyruvate ratio in diabetic rats, without an effect on blood glucose or glycated hemoglobin. AGE/ALEs, fluorescence and cross-linking of skin collagen increased approximately twofold in diabetic versus control rats after seven months of diabetes. Pyridoxamine caused a significant (25 to 50%) decrease the AGE/ALEs, carboxymethyllysine and carboxyethyllysine, crosslinking and fluorescence in skin collagen of diabetic rats, but did not affect pentosidine,Conclusions. Pyridoxamine inhibits the progression of renal disease, and decreases hyperlipidemia and apparent redox. imbalances in diabetic rats. Pyridoxamine and aminoguanidine had similar effects on parameters measured, supporting a mechanism of action involving AGE/ALE inhibition.