尿毒症毒素与心脏损伤的再认识

New insight into the uremic toxins and cardiac injury

心血管疾病(CVD)是慢性肾脏病(CKD),尤其是终末期肾病患者最常见的并发症及死亡原因之一。近年来,研究证实CKD患者及血液透析(HD)患者发生CVD及全因死亡率与蛋白结合毒素的蓄积密切相关。蛋白结合毒素是一类很难通过单纯HD清除的物质,大部分分子质量大于500 Da,与蛋白结合后导致蛋白自身分子结构、电荷甚至功能发生变化,抑或可能导致其他组织、器官损伤。目前研究相对较多的是同型半胱氨酸、硫酸吲哚酚、硫酸对甲酚等物质对肾脏及心血管的毒性,其可能的致病机制包括刺激内皮细胞或白细胞产生自由基,影响内皮细胞和白细胞的相互作用,损伤内皮细胞,促进血管平滑肌细胞增殖,导致动脉粥样硬化、心脏的纤维化等。

Cardiovascular disease （CVD） , the most common complication for chronic kidney disease, especially in patients with end-stage renal disease, but also is the leading cause of death. Recently, the protein-bound uremic toxins have been demonstrated that closely interrelated with cardiovascular mortality in CKD and/or dialysis patients. The protein- bound uremic toxins, the uremic toxics combined with albumin, most of them have an molecular weight （MW） 〉500 Da, which are poorly removed by currently standard dialysis strategies, may lead to the great change of the protein molecular structure itself, or even the function and the electricity, as well as injures to other organs or systems. More and more studies have demonstrated that the protein-bound uremic toxins, especially homocysteine, indoxyl sulfate and p-cresyl sulfate induce endothelial dysfunction and leukocyte activation, causing high oxidative stress. They also adversely affect the interaction between leukocytes and endothelium. Vascular smooth muscle cell （VSMC） prohferation, increased risk of atherosclerosis, and cardiac fibrosis may together explain the cardiovascular and renal toxicity of these protein-bound uremic toxins.