急性和慢性肾脏病小鼠模型中肾组织SFXNs表达下降

doi:10.16352/j.issn.1001-6325.2025.12.1541

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (12): 1541-1547.doi: 10.16352/j.issn.1001-6325.2025.12.1541

急性和慢性肾脏病小鼠模型中肾组织SFXNs表达下降

高立^1,2#, 王思懿^2,3#, 张敏菁², 赵琳², 徐哲明², 张根生², 严洁萍^1*

1.浙江省人民医院杭州医学院附属人民医院临床药学中心药学部,浙江杭州 310014;
2.浙江大学医学院附属儿童医院国家儿童健康与疾病临床医学研究中心,浙江杭州 310052;
3.浙江工业大学药学院药学系,浙江杭州 310014

收稿日期:2024-11-22 修回日期:2025-02-26 出版日期:2025-12-05 发布日期:2025-11-25
通讯作者: ^*yanjieping@hmc.edu.cn
作者简介:^#对本文有相同贡献
基金资助:
浙江省自然科学基金联合基金(LHDMY23H070007);浙江省医药卫生科技计划项目(2025KY011)

Decreased expression of SFXNs in renal tissues of mouse models of acute and chronic kidney disease

GAO Li^1,2#, WANG Siyi^2,3#, ZHANG Minjing², ZHAO Lin², XU Zheming², ZHANG Gensheng², YAN Jieping^1*

1. Department of Pharmacy, Center for Clinical Pharmacy, Zhejiang Provincial People′s Hospital, People′s Hospital Affiliated to Hangzhou Medical College, Hangzhou 310014;
2. Children′s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052;
3. Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China

Received:2024-11-22 Revised:2025-02-26 Online:2025-12-05 Published:2025-11-25
Contact: ^*yanjieping@hmc.edu.cn

摘要/Abstract

摘要： 目的探讨顺铂(Cis)或缺血再灌注(IR)诱导的急性肾损伤(AKI)与慢性肾脏病(CKD)小鼠模型中铁自噬-线粒体铁离子转运蛋白家族(SFXNs)的表达变化。方法将C57BL/6小鼠随机分为对照(control)组、Cis-AKI组、Cis-CKD组和假手术(sham)组、IR-AKI组、IR-CKD组。造模成功后收集小鼠的血清和肾组织样本。检测血清肌酐(Cr)和血尿素氮(BUN)水平;HE染色观察肾组织病理改变;Western blot检测肾SFXNs和肾损伤相关蛋白的表达。结果和对照组或假手术组相比,模型组血清中的BUN和Cr水平显著升高(P＜0.05),肾组织也有明显的病理损伤(P＜0.05),肾损伤标志蛋白肾损伤分子-1(KIM-1)、中性粒细胞明胶酶相关脂质转运蛋白(NGAL)和促凋亡蛋白Bax显著升高(P＜0.05),而抑凋亡蛋白Bcl-2显著下调(P＜0.05)。和对照组或假手术组相比,Cis-AKI组SFXN4显著下调(P＜0.05);Cis-CKD组和IR-AKI组SFXN4和SFXN5亚型均显著下调(P＜0.05);IR-CKD组SFXN的5个亚型均显著下调(P＜0.05)。结论顺铂或IR诱导了小鼠肾组织损伤和肾小管线粒体损伤,并影响了SFXN家族蛋白的不同表达变化,提示它们在不同肾损伤模型中起着不同作用。

关键词: 顺铂, 缺血再灌注, 急性肾损伤, 慢性肾脏病, 铁自噬-线粒体铁离子转运蛋白家族

Abstract: Objective To investigate the expression changes of iron autophagy-mitochondrial ferric ion transport protein families (SFXNs) in acute kidney injury (AKI) and chronic kidney disease (CKD) mouse models induced by cisplatin (Cis) and ischemia reperfusion (IR). Methods C57BL/6 mice were randomly divided into control group (control), Cis-AKI group, Cis-CKD group, sham-operated group (sham), IR-AKI group, and IR-CKD group. Serum and kidney tissue samples were collected from mice. Serum creatinine (Cr) and blood urea nitrogen (BUN) levels were detected. Pathological changes in renal tissues were observed by HE staining. Western blot was used to detect the expression of renal SFXNs and kidney injury related proteins. Results Compared with the control or sham group, the levels of BUN and Cr in the serum of the model group were significantly increased(P＜0.05), the renal tissue showed significant pathological damage, with the kidney injury molecule-1(KIM-1), neutrophil gelatinase-associated lipocalin(NGAL), and pro-apoptotic protein Bax significantly upregulated(P＜0.05), while the anti-apoptotic protein Bcl-2 was significantly downregulated (P＜0.05). Compared to the control or sham group, the Cis-AKI group showed a significant downregulation of SFXN4 (P＜0.05); The SFXN4 and SFXN5 subtypes were significantly downregulated in the IR-AKI group and Cis-CKD group (P＜0.05); All five subtypes of SFXN in the IR-CKD group were significantly downregulated (P＜0.05). Conclusions Cis or IR induces renal tissue damage and tubular mitochondrial injury in mice and affects the expression of SFXN family proteins, suggesting their potential role in renal injury of animal models.

Key words: cisplatin, ischemia reperfusion, acute kidney injury, chronic kidney disease, sideroflexins

中图分类号:

R363

高立, 王思懿, 张敏菁, 赵琳, 徐哲明, 张根生, 严洁萍. 急性和慢性肾脏病小鼠模型中肾组织SFXNs表达下降[J]. 基础医学与临床, 2025, 45(12): 1541-1547.

GAO Li, WANG Siyi, ZHANG Minjing, ZHAO Lin, XU Zheming, ZHANG Gensheng, YAN Jieping. Decreased expression of SFXNs in renal tissues of mouse models of acute and chronic kidney disease[J]. Basic & Clinical Medicine, 2025, 45(12): 1541-1547.

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急性和慢性肾脏病小鼠模型中肾组织SFXNs表达下降

Decreased expression of SFXNs in renal tissues of mouse models of acute and chronic kidney disease

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