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Role of dyslipidemia and AGE/ALE formation in theprogression of nephropathy and retinopathy inSTZ-diabetic rats

机译:血脂血症和年龄/芽面形成在STZ - 糖尿病大鼠肾病和视网膜病变中的作用

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We hypothesized that the beneficial effects of a variety of pharmacological agents on the progression of diabetic complications were mediated by a common pathway limiting the formation of advanced glycation and advanced iipoxidation end products (AGEs/ALEs) on protein. We studied the effects of the AGE/ALE inhibitor pyridoxamine (PM), the antioxidant vitamin E (VE) and the ACE inhibitor enalapril (EP) on the development of nephropathy and retinopathy in STZ-induced diabetic rats over 29 weeks. Blood giucose and glycohemoglobin were similar in all diabetic groups. Plasma lipids rose continuously in diabetic animals and only PM significantly attenuated this increase. Early nephropathy was indicated by increased plasma creatinine, and urinary albumin, protein and TGF-beta excretion in untreated rats. While all interventions limited renal damage to some extent, PM was the most effective, although the increased expression of renal laminin pi and fibronectin mRNA was normalized by all therapies. Measurement of retinal damage (acellular capillaries, vascular basement membrane-associated laminin) showed that only PM significantly limited signs of early retinopathy in diabetic rats. Only PM limited the increases in the AGE/ALEs in renal and retinal tissue, and in skin collagen, of diabetic rats. Our results suggest that limiting both dyslipidemia and AGE/ALE formation is required for maximum protection of renal and retinal function in the STZ-diabetic rat.
机译:我们假设各种药理剂对糖尿病并发症进展的有益效果是通过限制在蛋白质上的先进糖化和先进的碘化终产物(Ages / Ales)的形成的常见途径。我们研究了年龄/ ALE抑制剂吡哆胺(PM),抗氧化剂维生素E)和ACE抑制剂enalapril(EP)在29周内超过29周内促进糖尿病大鼠肾病和视网膜病变的发育的影响。所有糖尿病群中血giucose和甘油杂交蛋白相似。血浆脂质在糖尿病动物中连续升起,只有PM显着减弱这种增加。通过增加的血浆肌酐,尿白蛋白,蛋白质和TGF-Beta排泄,表明早期的肾病表明在未处理的大鼠中。虽然所有干预有​​限的肾脏损伤在某种程度上,PM是最有效的,但是通过所有疗法标准化肾层蛋白Pi和纤维连接蛋白mRNA的增加。视网膜损伤的测量(无细胞毛细血管,血管基底膜相关层粘蛋白)表明,只有PM在糖尿病大鼠中显着限制早期视网膜病变的迹象。只有PM限制肾病组织和皮肤胶原蛋白的年龄/啤酒的增加,糖尿病大鼠。我们的研究结果表明,在STZ - 糖尿病大鼠中最大限度地保护肾病和视网膜功能的最大保护需要限制血脂血症和年龄/淋污染。

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