内科理论与实践2026，Vol.21Issue(2)：124-131,8.DOI:10.16138/j.1673-6087.2026.02.04
C57BL/6亚品系在多柔比星诱导FSGS模型中的差异研究
Comparison of doxorubicin-induced FSGS models across C57BL/6 substrains
摘要
Abstract
Objective To investigate the optimal protocol for a doxorubicin-induced chronic kidney disease mouse model used for studying human focal segmental glomerulosclerosis(FSGS).Methods C57BL/6J and C57BL/6N mice were randomly assigned using a random number sequence into control groups(J0 and N0,24 mice each)and FSGS model groups(J1,J2,N1,and N2,24 mice each).J1 and N1 groups received a single tail vein injection of 15 mg/kg doxorubicin,J2 and N2 groups received two injections(with a two-week interval),and J0 and N0 groups received an equal volume of 0.9%sodium chloride injection.The overall condition and body weight changes of the mice were observed,and general data were recorded.Urine was collected to evaluate proteinuria through urinary protein and urinary creatinine.Kidney tissue proteins were extracted for Western blot analysis to detect the expression of podocyte marker proteins.Kidney histopathological manifestations were observed using hematoxylin-eosin staining,periodic acid-Schiff staining and transmission electron microscopy.Results After modeling,C57BL/6N mice showed worse general condition and more significant weight loss than C57BL/6J mice(P<0.001).In both strains,mice receiving two doxorubicin injections showed poorer general condition and more pronounced weight loss(P<0.001).The urinary protein-to-creatinine ratio in the doxorubicin-injected groups of both C57BL/6J and C57BL/6N was higher than that in the control groups at all time points(P<0.05).In the single-injection C57BL/6J group,the expression of some podocyte marker proteins[synaptopodin,Wilms tumor protein 1(WT1)]showed no significant changes,while in the two-injection group,the expression levels of podocyte marker proteins(nephrin,synaptopodin,podocalyxin,WT1,α-tubulin,podocin)were all lower than those in the control group.Both single-and two-injection C57BL/6N groups showed lower expression level of podocyte marker proteins than that in the control group,with more significant decreases in the two-injection group(P<0.05).Light and electron microscopy both confirmed successful modeling in the single-and two-injection C57BL/6N groups,with more significant pathological changes in the two-injection group.Conclusions In the doxorubicin-induced FSGS model in C57BL/6 mice,the C57BL/6N substrain outperforms C57BL/6J substrain in modeling efficacy.The recommended optimal modeling protocol for FSGS is the single tail vein injection of 15 mg/kg doxorubicin in C57BL/6N mice.关键词
局灶节段性肾小球硬化/多柔比星/足细胞/C57BL/6J/C57BL/6NKey words
focal segmental glomerulosclerosis/doxorubicin/podocyte/C57BL/6J/C57BL/6N分类
医药卫生引用本文复制引用
孙羽斐,刘爽,李慧凛,蒋更如..C57BL/6亚品系在多柔比星诱导FSGS模型中的差异研究[J].内科理论与实践,2026,21(2):124-131,8.基金项目
国家自然科学基金(82170713)、上海市卫生健康委员会科研项目(202040293)、上海市浦东新区卫生健康系统医学领先人才培养计划(PWRl2024-01)、上海市浦东新区卫生健康委员会学科建设计划(PWZzb2022-03) （82170713）
