淋巴管新生在糖尿病肾病发病中的作用研究进展

Research progress in roles of lymphangiogenesis in diabetic nephropathy

淋巴管新生在糖尿病肾病(DN)发病中起着重要作用。高糖引起的晚期糖基化终产物增多和氧化应激反应增强是促进淋巴管新生的重要因素。全身高血糖和脂质肾毒性促使肾组织内慢性炎症的发生,从而促进促炎因子白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的增加,刺激肾细胞分泌转化生长因子β(TGF-β),同时募集巨噬细胞增加促炎因子和TGF-β的分泌。研究表明,TGF-β,IL-1β和TNF-α均可损伤人近端肾小管上皮细胞,使其分泌血管内皮生成因子C(VEGF-C),而VEGF-C是诱导淋巴管新生主要细胞因子之一。此外,由于新生的淋巴管通透性强、无序性扩张等特点导致淋巴液外流增多,致使免疫细胞抑制炎症失败,加剧肾慢性炎症,从而进一步促进DN的纤维化进程。

Lymphatic vessel regeneration plays an important role in the pathogenesis of diabetic nephropathy.The increase of advanced glycation end products and the enhancement of oxidative stress induced by high glucose are important factors of lymphangiogenesis.Systemic hyperglycemia and lipid nephrotoxicity promote the occurrence of chronic inflammation in renal tissue,thus promoting the increase of proinflammatory factors interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α),stim⁃ulating renal cells to secrete transforming growth factor-β(TGF-β),and recruiting macrophages to increase the secretion of proinflammatory factors and TGF-β.Studies have shown that TGF-β,IL-1βand TNF-αcan damage human proximal renal tubular epithelial cells and make them secrete vascular endothelial growth factor C,which is one of the main cytokines that induce lymphangiogenesis.In addi⁃tion,due to the strong permeability and disorderly expansion of new lymphatic vessels,the outflow of lymph increases,which leads to the failure of immune cells to clear inflammation,aggravates chronic kidney inflammation and promotes the fibrosis process of diabetic nephropathy.