外泌体在糖尿病肾病早期诊断和治疗中的研究进展

Progress on exosomes in early diagnosis and treatment of diabetic kidney disease

随着糖尿病发病率的升高,目前糖尿病肾病(DKD)已成为慢性肾脏病的首要病因之一,除肾脏病理活检外,通过血清、尿液特异标志物等获得糖尿病肾病早期诊断对改善患者预后有重要意义。外泌体是一种细胞外囊泡,可参与细胞间信息交流、免疫调节等病理生理过程。由于外泌体具有易获取、稳定性高、诊断特异性高等优点,目前已成为糖尿病肾病病理生理机制的探索及早期诊断的研究热点。间充质干细胞外泌体可降低糖尿病肾病肾组织内白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)等炎症因子表达,抑制炎症反应、改善肾脏纤维化,已有临床试验证实干细胞治疗对糖尿病患者有保护肾脏的作用。近年来研究发现,细胞自噬作用减弱是糖尿病肾病发生及发展的重要病理生理机制之一,外泌体可通过雷帕霉素靶蛋白(mTOR)途径调节细胞自噬,减轻糖尿病肾病足细胞损害,因此自噬相关基因或蛋白可成为糖尿病肾病潜在的治疗靶点。

With the increasing incidence of diabetes mellitus,diabetic kidney disease(DKD)has become one of the leading causes of chronic kidney disease.Apart from kidney biopsy,early diagnosis of diabetic nephropathy through specific serum and urine markers is of great significance to improve the prognosis of patients.Exosomes are extracellular vesicles that participate in cell communication and immune regulation.Due to the advantages of easy access,high stability,and high specificity,exosomes have become a focus for understanding the pathological mechanism of diabetic nephropathy.Mesenchymal stem cell exosome can reduce the expression of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and other inflammatory factors in the renal tissue of diabetic nephropathy,inhibit inflammatory response,and improve renal fibrosis.Clinical trials have confirmed that stem cell therapy can protect the kidney in diabetic patients.Recent studies have found that decreased autophagy is one of the important pathophysiological mechanisms in the occurrence and development of diabetic nephropathy.Exosomes can regulate autophagy through the mammalian target of rapamycin(mTOR)pathway to reduce the damage of diabetic nephropathy podocytes.Therefore,autophagy related genes or proteins can be potential therapeutic targets of diabetic nephropathy.