内源性果糖在糖尿病肾病小管损伤中的作用及其机制

Role and mechanism of endogenous fructose in renal tubular injury in diabetic nephropathy

在糖尿病血糖升高的情况下,葡萄糖代谢的多元醇途径被激活,内源性果糖生成增加。果糖在肝细胞和肾小管上皮细胞等靶细胞中代谢时,可快速而不可逆地引起细胞内三磷酸腺苷(ATP)消耗和嘌呤核苷酸转换,并生成终产物尿酸,这一反应过程也称为果糖-尿酸轴。尿酸可直接作用于肾小管上皮细胞和管周内皮细胞,引起肾小管损伤。由于糖尿病性肾小管损伤较肾小球损伤出现更早,且与肾功能进行性减退的关系更为密切,果糖-尿酸轴可能是糖尿病肾病(DN)的一种全新而重要的发病机制,对于发掘防治DN的新疗法、改善DN的预后具有重要意义。

In diabetes,hyperglycemia is associated with activation of the polyol pathway,in which fructose is endogenously overproduced.When fructose is metabolized in hepatocytes and tubular epithelial cells,ATP depletion and purine nucleotide turnover occur rapidly and irreversibly,and uric acid is eventually generated.The metabolism of fructose to uric acid is also known as the fructose-uric acid axis.Uric acid derived from endogenous fructose could directly impair renal tubular epithelial cells and peritubular capillary endothelial cells,resulting in diabetic tubulopathy.In the course of diabetic nephropathy,tubular injury may be induced earlier than glomerular injury and may be more closely associated with renal function.For this reason,the fructose-uric acid axis as a novel mechanism for the development of diabetic tubular injury provides new insights into the pathogenesis and treatment of diabetic nephropathy.