Df-5化合物延缓大鼠糖尿病肾病的发展

A. Spasov, O. Zhukovskaya, A. I. Rashchenko, A. A. Brigadirova, R. Litvinov, N. A. Gurova, A. Smirnov, N. G. Pan’shin, H. S. Abbas, A. S. Morkovnik
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摘要

晚期糖基化终产物在糖尿病并发症的发展中起着重要作用,因此减缓糖基化蛋白交联的形成已被认为是治疗血管性糖尿病并发症并防止其发展的潜在治疗选择。本研究旨在评估新型抗交联剂DF-5对链脲霉素诱导的糖尿病大鼠肾脏晚期糖基化终产物和胶原蛋白含量、体重、血糖和糖化血红蛋白水平以及早期肾脏疾病发展的影响。材料和方法。40只雄性Sprague-Dawley大鼠被用于研究。诱导糖尿病2个月后,研究物质每天1次灌胃,连续28天(12.5 mg/kg)。测量包括血糖和糖化血红蛋白水平的评估,肾功能的评估,以及肾脏的组织学和免疫组织化学染色结果。反复灌胃DF-5 30天可显著降低血液中HbA1c水平,但不影响空腹血糖水平。DF-5化合物通过限制肾小球和小管的损伤,显著减少了实验动物的蛋白尿,防止了肾脏损伤。研究发现,DF-5抑制链脲佐菌素诱导的糖尿病肾病大鼠早期肾功能障碍的进展。这与肾脏中晚期糖基化终产物的积累减少有关,并伴有肾脏形态和功能的改善。获得的结果为研究人员提供了治疗糖尿病肾病和可能的其他糖尿病并发症的额外治疗选择。
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DF-5 COMPOUND DELAYS DEVELOPMENT OF DIABETIC NEPHROPATHY IN RATS
Advanced glycation end-products play an important role in the development of diabetic complications, so slowing down of glycated proteins’ cross-links formation have been suggested as a potential therapeutic option for the treatment of vascular diabetic complications and preventing their progression.The aim of the work was to assess the influence of novel anticrosslinking agent DF-5 on the renal advanced glycation end-products and collagen contents, body weight, blood glucose and glycated hemoglobin levels and the development of early renal disease in streptozotocin-induced diabetic rats.Materials and methods. 40 male Sprague-Dawley rats were used in the study. Two months after inducing diabetes, the study substance was administered intragastrically once a day for 28 days (12.5 mg/kg). Measurements included the assessment of blood glucose and HbA1c levels, the evaluation of the renal function, and the results of histology and immunohistochemical staining of kidneys.Results. A repeated intragastric administration of DF-5 for 30 days significantly reduced the level of HbA1c in the blood, but did not affect the level of fasting blood glucose. DF-5 compound significantly reduced proteinuria and prevented kidney damage in experimental animals by limiting damage of the glomeruli and tubules. It was found that DF-5 inhibits the progression of an early renal dysfunction in rats with streptozotocin-induced diabetic nephropathy. This was associated with a decreased accumulation of advanced glycation end-products in the kidney, accompanied by the improvement of both renal morphology and function.Conclusion. The results obtained provide investigators with additional therapeutic options for the treatment of diabetic nephropathy and possibly other complications of diabetes.
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