Rhodojaponin VI ameliorates podocyte injury related with MDM2/Notch1 pathway in rat experimental membranous nephropathy.

IF 2.4 4区医学 Q2 UROLOGY & NEPHROLOGY

Nephrology Pub Date : 2024-09-01 Epub Date: 2024-07-16 DOI:10.1111/nep.14337

Anni Song, Ruiwei Yan, Yue Qiu, Xingjie Yin, Jing Xiong, Guangmin Yao, Chun Zhang

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引用次数: 0

Abstract

Aim: Rhodojaponin VI (R-VI) is the key compound of Rhododendron molle G. Don (Ericaceae) (RM) with effective clinical application in rheumatoid arthritis and chronic glomerulonephritis. In our study, we tried to explore the effect of R-VI on the rat model of membranous nephropathy.

Methods: The rat model of passive heymann nephritis (PHN) was established by injecting sheep anti-rat Fx1A serum at a single dose through the tail. The rats were orally administered R-VI (0.02 mg/kg) or FK506 (1 mg/kg) 1 day before PHN induction, which was kept for 4 weeks. Urine and blood samples as well as kidney tissue were collected for analysis. C5b-9-induced human podocyte cell (HPC) was employed for experiments in vitro.

Results: R-VI could alleviate glomerulonephritis progression and podocyte injury in PHN rats, as indicated by the decreased proteinuria and the elevated level of albumin, accompanied with reduced immune deposits, reversed podocyte injury in the kidneys. Furthermore, R-VI suppressed murine double minute 2 (MDM2) expression without the alteration in the protein level of p53 and decreased Notch1 expression independent of Numb regulation. Pre-treatment with R-VI in C5b-9-induced HPC blocked MDM2/Notch1 signalling pathway.

Conclusion: Thus, R-VI ameliorates podocyte injury in rats with PHN, which was probably related with MDM2/Notch1 signalling pathway.

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红豆皂苷 VI 可改善大鼠实验性膜性肾病中与 MDM2/Notch1 通路相关的荚膜细胞损伤。

目的：Rhodojaponin VI（R-VI）是杜鹃花科植物杜鹃花（Rhododendron molle G. Don，Ericaceae）（RM）的主要化合物，临床上可有效治疗类风湿性关节炎和慢性肾小球肾炎。本研究试图探讨 R-VI 对膜性肾病大鼠模型的影响：方法：通过尾部注射单剂量羊抗鼠 Fx1A 血清，建立大鼠被动性海曼肾炎（PHN）模型。大鼠在 PHN 诱导前 1 天口服 R-VI（0.02 毫克/千克）或 FK506（1 毫克/千克），持续 4 周。收集尿液和血液样本以及肾脏组织进行分析。采用 C5b-9 诱导的人荚膜细胞（HPC）进行体外实验：结果：R-VI 可以缓解 PHN 大鼠肾小球肾炎的进展和荚膜细胞损伤，表现为蛋白尿减少、白蛋白水平升高、免疫沉积物减少、肾脏荚膜细胞损伤逆转。此外，R-VI 还能抑制小鼠双分 2（MDM2）的表达，而不会改变 p53 的蛋白水平，并能降低 Notch1 的表达，这与 Numb 的调控无关。在 C5b-9 诱导的 HPC 中预处理 R-VI 可阻断 MDM2/Notch1 信号通路：因此，R-VI 可改善 PHN 大鼠荚膜细胞损伤，这可能与 MDM2/Notch1 信号通路有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nephrology 医学-泌尿学与肾脏学

CiteScore

4.50

自引率

4.00%

发文量

128

审稿时长

4-8 weeks

期刊介绍： Nephrology is published eight times per year by the Asian Pacific Society of Nephrology. It has a special emphasis on the needs of Clinical Nephrologists and those in developing countries. The journal publishes reviews and papers of international interest describing original research concerned with clinical and experimental aspects of nephrology.