Abstract：
An arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis in uremic patients, yet its dysfunction poses a significant clinical challenge. Venous stenosis, primarily caused by venous neointimal hyperplasia, is a key factor in the failure of vascular access. During vascular access dysfunction, endothelial cells (ECs) transform mechanical stimuli into intracellular signals and interact with vascular smooth muscle cells. Tanshinone IIA, an important compound derived from Salvia miltiorrhiza, has been widely used to treat cardiovascular diseases. However, its role in modulating ECs under uremic conditions remains incompletely understood. In this research, ECs were exposed to sodium tanshinone IIA sulfonate (STS) and subjected to shear stress and uremic conditions. The results indicate that STS can reduce the suppressive effects on the expression of NF-κB p65, JNK and Collagen I in uremia-induced ECs. Moreover, the downregulation of NF-κB p65, JNK and Collagen I can be enhanced through the inhibition of ERK1/2 and the upregulation of Caveolin-1. These findings suggest that tanshinone IIA may improve EC function under uremic conditions by targeting the Caveolin-1/ERK1/2 pathway, presenting tanshinone IIA as a potential therapeutic agent against AVF immaturity caused by EC dysfunction.
摘要：
动静脉瘘（AVF）是尿毒症患者血液透析的首选血管通路，然而，其功能障碍构成了重大的临床挑战。静脉狭窄,主要由静脉新生内膜增生引起，是血管通路失败的关键因素。在血管通路功能障碍期间，内皮细胞（EC）将机械刺激转化为细胞内信号并与血管平滑肌细胞相互作用。丹参酮IIA,一种来自丹参的重要化合物，已被广泛用于治疗心血管疾病。然而,其在尿毒症条件下调节ECs的作用尚不完全清楚。在这项研究中,将EC暴露于丹参酮IIA磺酸钠（STS）并经受剪切应力和尿毒症条件。结果表明，STS可以降低尿毒症诱导的ECs对NF-κBp65，JNK和I型胶原表达的抑制作用。此外，通过抑制ERK1/2和上调Caveolin-1，可以增强NF-κBp65，JNK和胶原蛋白I的下调。这些结果表明，丹参酮IIA可能通过靶向小窝蛋白-1/ERK1/2途径改善尿毒症条件下的EC功能，提出丹参酮IIA作为一种潜在的治疗药物，用于治疗由EC功能障碍引起的AVF不成熟。
