江苏大学学报（医学版）2026，Vol.36Issue(1)：36-43,8.DOI:10.13312/j.issn.1671-7783.y250040
HucMSC-sEVs通过抑制肾小管上皮细胞坏死性凋亡缓解糖尿病肾病大鼠肾损伤
HucMSC-sEVs alleviate renal injury in diabetic nephropathy rats by inhibiting necroptosis of renal tubular epithelial cells
摘要
Abstract
Objective:To investigate the therapeutic effects and underlying mechanisms of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles(HucMSC-sEVs)on renal injury in diabetic kidney disease(DKD)rats.Methods:HucMSCs were isolated,cultured,and used to extract HucMSC-sEVs from their culture supernatant.A DKD rat model was induced by a high-fat diet combined with STZ injection.After successful modeling validation,rats were randomized into the DKD group and the HucMSC-sEVs group,with normal rats as controls.At 8 weeks,HucMSC-sEVs were injected via the tail vein.After 24 weeks,kidney tissues were collected.Renal histopathology was assessed by HE staining,while Masson staining was employed to evaluate collagen deposition.The expression levels of necroptosis markers(p-RIPK1/RIPK1,p-RIPK3/RIPK3,and p-MLKL/MLKL)were quantified using qRT-PCR,Western blotting,and immunohistochemical staining.NRK-52E cells were treated with high glucose and HucMSC-sEVs.Transmission electron microscopy was used to observe necrotic phenomena in NRK-52E cells,and the expression levels of necroptosis marker proteins such as p-RIPK1/RIPK1,p-RIPK3/RIPK3,and p-MLKL/MLKL were detected by Western blotting and qRT-PCR.Results:Compared with the control group,the glomerular basement membrane in the DKD group rats was significantly thickened,and the interstitium exhibited fibrotic characterization,with a marked increase in the expression of necroptosis marker proteins.After treatment with HucMSC-sEVs,the pathological damage and fibrosis degree of the rat kidney tissues were alleviated,and the expression of necroptosis execution proteins was reduced.In vitro experiments revealed that high glucose-treated NRK-52E cells exhibited necrotic features including mitochondrial cristae fragmentation,endoplasmic reticulum dilation,and elevated expression of necroptosis markers(p-RIPK1/RIPK1,p-RIPK3/RIPK3,and p-MLKL/MLKL).Treatment with HucMSC-sEVs significantly attenuated these cellular alterations and reduced the expression levels of necroptosis-related proteins.Conclusion:HucMSC-sEVs can improve renal function and delay the progression of DKD in rats,and the mechanism may be attributed to the inhibition of necroptosis of renal tubular epithelial cells.关键词
人脐带间充质干细胞/细胞外囊泡/糖尿病肾病/坏死性凋亡Key words
human umbilical cord mesenchymal stem cells/small extracellular vesicles/diabetic kidney disease/necroptosis分类
医药卫生引用本文复制引用
薛玲玲,金灿,钱晖..HucMSC-sEVs通过抑制肾小管上皮细胞坏死性凋亡缓解糖尿病肾病大鼠肾损伤[J].江苏大学学报（医学版）,2026,36(1):36-43,8.基金项目
国家自然科学基金资助项目(82172102) （82172102）
镇江市外泌体基础与转化应用高技术研究重点实验室(SS2018003) （SS2018003）
