Page 42 - 南京医科大学自然版

南京医科大学学报（自然科学版） 第46卷第5期
·664 · Journal of Nanjing Medical University（Natural Sciences） 2026年5月

·基础研究·

tRF⁃AsnGTT⁃33减轻阿霉素肾病小鼠足细胞损伤的机制研究

徐明星，黄 婵，宁蓓蓓，施会敏，甘卫华 *
南京医科大学第二附属医院儿肾科，江苏 南京 210003

［摘 要］ 目的：探讨 tRNA 衍生片段 AsnGTT⁃33（tRNA⁃derived fragment AsnGTT⁃33，tRF⁃AsnGTT⁃33）在阿霉素（adriamycin，
ADR）肾病小鼠足细胞损伤中的作用和机制。方法：尾静脉一次性注入ADR（10 mg/kg），构建ADR肾病小鼠模型，尾静脉注射
tRF⁃AsnGTT⁃33腺相关病毒（adeno⁃associated virus，AAV）0.5 mL/只实现体内过表达，采用肌氨酸氧化酶法检测小鼠血清肌酐
（serum creatinine，Scr）、脲酶法检测血尿素氮（blood urea nitrogen，BUN）、苏木精和伊红染色（hematoxylin and eosin staining，HE）
和过典酸⁃雪芙染色（periodic acid⁃schiff stain，PAS）观察肾小球及肾小管损伤程度，并通过qPCR 和Western blot 分析足细胞标
志物Nephrin和Podocin的表达变化。体外以1 mg/L ADR 诱导足细胞损伤，转染tRF⁃AsnGTT⁃33 mimic后，通过qPCR和Western
blot 检测细胞内 nephrin 和 podocin 表达变化。基于 miRDB 数据库预测 RAB21 为靶基因，检测足细胞及小鼠肾脏组织中 tRF⁃
AsnGTT⁃33 过表达对 RAB21 表达的影响。结果：ADR 肾病小鼠肾组织 tRF⁃AsnGTT⁃33 表达显著下调，伴随 Scr、BUN 升高，
nephrin和podocin表达降低，肾脏病理损伤加重，如肾小球基底膜增厚、肾小管内可见蛋白管型、间质纤维化等；tRF⁃AsnGTT⁃33
过表达可显著降低Scr及BUN水平，减轻病理损伤，上调Nephrin和Podocin的表达。ADR诱导的足细胞中tRF⁃AsnGTT⁃33表达
下调，且Nephrin和Podocin表达下降，tRF⁃AsnGTT⁃33过表达后Nephrin和Podocin表达升高。tRF⁃AsnGTT⁃33过表达后足细胞
及小鼠肾脏组织中RAB21表达均显著下调。结论：tRF⁃AsnGTT⁃33可能通过靶向调控 RAB21减轻ADR诱导的足细胞损伤，为
寻找慢性肾脏病治疗靶点提供理论依据。
［关键词］ 阿霉素肾病；足细胞；细胞凋亡；tRF⁃AsnGTT⁃33；RAB21
［中图分类号］ R329 ［文献标志码］ A ［文章编号］ 1007⁃4368（2026）05⁃664⁃09
doi：10.7655/NYDXBNSN250685

Mechanism of podocyte injury attenuation by tRF⁃AsnGTT⁃ 33 in adriamycin⁃induced in

nephropathy mice
XU Mingxing，HUANG Chan，NING Beibei，SHI Huimin，GAN Weihua *
Department of Pediatric Nephrology，the Second Affiliated Hospital of Nanjing Medical University，Nanjing 210003，
China

［Abstract］ Objective：To investigate the role and mechanism of the tRNA⁃derived fragment AsnGTT⁃ 33（tRF⁃AsnGTT⁃ 33）in
podocyte injury within a murine model of adriamycin（ADR）⁃induced nephropathy. Methods：An ADR nephropathy mouse model was
established via a single tail vein injection of ADR（10 mg/kg）. tRF⁃AsnGTT⁃33 adeno⁃associated virus（AAV）（0.5 mL per mouse）was
administered via tail vein to achieve in vivo overexpression. Renal function was assessed by measuring serum creatinine（Scr）levels
using the sarcosine oxidase method and blood urea nitrogen（BUN）levels using the urease method. Renal pathological injury was
evaluated by hematoxylin and eosin staining（HE）and periodic acid⁃schiff staining（PAS）to observe glomerular and tubular damage.
The mRNA and protein expression levels of the podocyte markers nephrin and podocin were analyzed by quantitative PCR（qPCR）and
Western blot，respectively. In vitro，podocyte injury was induced by 1 mg/L ADR. Following transfection with a tRF⁃AsnGTT⁃33 mimic，
the expression levels of nephrin and podocin were detected by qPCR and Western blot. The miRDB database was used to predict Ras⁃
related protein RAB21 as a potential target gene. The effect of tRF⁃AsnGTT⁃33 overexpression on RAB21 expression was subsequently
examined in both cultured podocytes and mouse renal tissues. Results：Renal tissues from ADR nephropathy mice exhibited
significantly downregulated tRF⁃AsnGTT⁃33 expression，accompanied by markedly elevated Scr and BUN levels，reduced expression of
nephrin and podocin，and aggravated renal pathological injury，including thickening of the glomerular basement membrane，

［基金项目］ 国家自然科学基金（82400864）；南京市卫生科技发展专项（YKK23288，YKK23289）
通信作者（Corresponding author），E⁃mail：weihuagan@njmu.edu.cn（ORCID：0000⁃0002⁃4649⁃2368）
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