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在阿霉素诱导的肾病综合征大鼠模型中通过抑制B细胞活化因子对足细胞病的保护作用

Protective Effects of on Podocythopathies Through B-Cell-Activating Factor Inhibition in Doxorubicin-Induced Nephrotic Syndrome Rat Model.

作者信息

Kardani Astrid K, Fitri Loeki E, Samsu Nur, Subandiyah Krisni

机构信息

Doctoral Program in Medical Sciences, Faculty of Medicine Universitas Brawijaya, Malang 65145, East Java, Indonesia.

Nephrology Division, Department of Pediatric, Faculty of Medicine Universitas Brawijaya Malang 65145/Dr. Saiful Anwar General Hospital, Malang 65111, East Java, Indonesia.

出版信息

Biomedicines. 2025 Mar 14;13(3):719. doi: 10.3390/biomedicines13030719.

DOI:10.3390/biomedicines13030719
PMID:40149694
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11940115/
Abstract

: Nephrotic syndrome, a glomerular disease caused by podocyte dysfunction, is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Current treatment relies on corticosteroids, which carry the risk of long-term side effects. has potential as an adjunct therapy for immune-mediated kidney injury. This study aims to evaluate the effects of extracts on anti-nephrin IgG, IL-4, and podocytopathy through BAFF inhibition in a doxorubicin-induced nephrotic syndrome rat model. : This experimental study involved 36 Sprague-Dawley rats divided into control and treatment groups. The treatment groups received extract at doses of 500 mg/kgBW, 1500 mg/kgBW, and 2500 mg/kgBW, or in combination with prednisone, alongside a group receiving prednisone monotherapy. Podocytopathy was assessed using proteinuria, nephrin, podocalyxin, and GLEPP-1. Proteinuria was measured using spectrophotometry. Serum BAFF levels, renal IL-4, urinary nephrin, and urinary podocalyxin were analyzed using ELISA. Renal nephrin, renal podocalyxin, GLEPP-1, and BAFF expression were evaluated by immunofluorescence microscopy. The data were analyzed using SPSS 25. : The results showed significant reductions in proteinuria, serum BAFF levels, renal BAFF expression, anti-nephrin IgG, IL-4, urinary nephrin, and urinary podocalyxin, along with significant increases in GLEPP-1, renal nephrin, and renal podocalyxin expression, in all treatment groups compared to the nephrotic syndrome control group. The combination of at 2500 mg/kgBW with prednisone demonstrated the best effects. : shows promise as an adjuvant therapy for nephrotic syndrome by improving podocytopathy through BAFF inhibition. Further research is needed to evaluate its long-term safety, optimize dosing, and explore clinical applications in humans.

摘要

肾病综合征是一种由足细胞功能障碍引起的肾小球疾病,其特征为蛋白尿、低白蛋白血症、水肿和高脂血症。目前的治疗依赖于皮质类固醇,存在长期副作用风险。[某物质]作为免疫介导性肾损伤的辅助治疗具有潜力。本研究旨在通过在阿霉素诱导的肾病综合征大鼠模型中抑制B细胞活化因子(BAFF),评估[某物质]提取物对抗nephrin IgG、白细胞介素-4(IL-4)和足细胞病变的影响。:本实验研究涉及36只Sprague-Dawley大鼠,分为对照组和治疗组。治疗组分别接受500 mg/kg体重、1500 mg/kg体重和2500 mg/kg体重剂量的[某物质]提取物,或与泼尼松联合使用,同时设一组接受泼尼松单药治疗。使用蛋白尿、nephrin、足细胞表面蛋白和肾小球富含脯氨酸蛋白-1(GLEPP-1)评估足细胞病变。采用分光光度法测量蛋白尿。使用酶联免疫吸附测定(ELISA)分析血清BAFF水平、肾IL-4、尿nephrin和尿足细胞表面蛋白。通过免疫荧光显微镜评估肾nephrin、肾足细胞表面蛋白、GLEPP-1和BAFF表达。使用SPSS 25分析数据。:结果显示,与肾病综合征对照组相比,所有治疗组的蛋白尿、血清BAFF水平、肾BAFF表达、抗nephrin IgG、IL-4、尿nephrin和尿足细胞表面蛋白均显著降低,同时GLEPP-1、肾nephrin和肾足细胞表面蛋白表达显著增加。2500 mg/kg体重的[某物质]与泼尼松联合使用效果最佳。:[某物质]通过抑制BAFF改善足细胞病变,有望作为肾病综合征的辅助治疗。需要进一步研究评估其长期安全性、优化给药剂量并探索在人类中的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11940115/9e94f24f937a/biomedicines-13-00719-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11940115/30a4ec4d7b47/biomedicines-13-00719-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11940115/9e94f24f937a/biomedicines-13-00719-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11940115/30a4ec4d7b47/biomedicines-13-00719-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11940115/bfe4517748d5/biomedicines-13-00719-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11940115/ffe03cfd677d/biomedicines-13-00719-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11940115/db9c1c5a8792/biomedicines-13-00719-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11940115/c08f967fab18/biomedicines-13-00719-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd95/11940115/9e94f24f937a/biomedicines-13-00719-g006.jpg

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