红景天苷 VI 通过调控 MDM2/Notch1 通路改善大鼠实验性膜性肾病足细胞损伤。
Rhodojaponin VI ameliorates podocyte injury related with MDM2/Notch1 pathway in rat experimental membranous nephropathy.
机构信息
Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
出版信息
Nephrology (Carlton). 2024 Sep;29(9):555-564. doi: 10.1111/nep.14337. Epub 2024 Jul 16.
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.
目的
基源为杜鹃花科植物密枝杜鹃（Rhododendron molle G. Don）的罗地奥酮 VI（R-VI）在类风湿关节炎和慢性肾小球肾炎的临床应用中具有显著疗效，是其发挥作用的关键化合物。本研究旨在探讨 R-VI 对大鼠膜性肾病模型的影响。
方法
通过尾静脉一次性注射绵羊抗大鼠 Fx1A 血清建立大鼠被动性 Heymann 肾炎（PHN）模型。在 PHN 诱导前 1 天，大鼠分别给予 R-VI（0.02mg/kg）或 FK506（1mg/kg）灌胃，持续 4 周。收集尿液和血液样本以及肾组织进行分析。体外实验采用 C5b-9 诱导的人足细胞（HPC）。
结果
R-VI 可减轻 PHN 大鼠的肾小球肾炎进展和足细胞损伤，表现为蛋白尿减少和白蛋白水平升高，同时免疫沉积减少，肾脏足细胞损伤得到逆转。此外，R-VI 抑制了鼠双微体 2（MDM2）的表达，而不改变 p53 的蛋白水平，并降低 Notch1 的表达，而不依赖于 Numb 调节。在 C5b-9 诱导的 HPC 中预先给予 R-VI 可阻断 MDM2/Notch1 信号通路。
结论
因此，R-VI 可改善 PHN 大鼠的足细胞损伤，其机制可能与 MDM2/Notch1 信号通路有关。
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