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姜黄素在局灶节段性肾小球硬化小鼠模型中的肾保护作用

Nephroprotective Effects of Curcumin in Murine Models of Focal and Segmental Glomerulosclerosis.

作者信息

Husain Sufia, Kamal Bayoumy Nervana Mustafa, Noor Fatima, Hagar Hanan, Husain Sufia

机构信息

Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

King Saud University-Medical City, Riyadh, Saudi Arabia.

出版信息

Pharmacology. 2025;110(4):221-230. doi: 10.1159/000543293. Epub 2025 Jan 8.

DOI:10.1159/000543293
PMID:39778541
Abstract

INTRODUCTION

This study aims to explore the reno-protective effect of curcumin in focal and segmental glomerulosclerosis (FSGS) in murine models, a common chronic glomerulopathy that leads to end-stage renal disease.

METHODS

Adult Wistar rats were used in this experiment. One group was treated with intravenous Adriamycin (ADR) injection to induce FSGS similar to that seen in humans and a second group was co-administered ADR and curcumin (ADR-CUR). Saline-treated rats served as controls. Renal injury was assessed by measuring the levels of serum creatinine, blood urea nitrogen (BUN), triglyceride, and urinary protein. The homogenates of renal cortex were used to estimate the renal content of the inflammatory marker tumor necrosis factor-a (TNF-a); oxidative stress marker malonaldehyde (MDA); and two antioxidants superoxide dismutase (SOD) and reduced glutathione (GSH). In addition, the rat kidneys were harvested by ends of week 8 and week 12 and examined for histological abnormalities.

RESULTS

The ADR-treated rats showed biochemical and histological evidence of FSGS, in the form of proteinuria, elevated serum creatinine, BUN, and triglycerides, elevated renal TNF-a and MDA, and segmental glomerulosclerosis. The ADR-CUR-treated rats showed significant correction of all these variables. Co-administration with curcumin resulted in improvement of the proteinuria, serum creatinine, BUN, and triglyceride. The renal tissue levels of antioxidants SOD and GSH increased and that of TNF-a and MDA decreased and the histology revealed reduction in the extent of segmental glomerulosclerosis. The FSGS-associated renal damage was notably antagonized by curcumin treatment.

CONCLUSION

Our findings confirm the reno-protective effects of curcumin as a potential therapeutic agent in protection against the progression of FSGS and indicate that it is mitigated by inhibition of oxidant injury and inflammation and also by promotion of antioxidants. Curcumin ameliorated the ADR-induced FSGS in murine models. It may be a promising compound in the treatment of FSGS in human subjects. More human studies are needed to further elucidate its effects in FSGS.

摘要

引言

本研究旨在探讨姜黄素对小鼠局灶节段性肾小球硬化(FSGS)模型的肾脏保护作用,FSGS是一种常见的慢性肾小球疾病,可导致终末期肾病。

方法

本实验使用成年Wistar大鼠。一组通过静脉注射阿霉素(ADR)诱导类似于人类所见的FSGS,另一组同时给予ADR和姜黄素(ADR-CUR)。用生理盐水处理的大鼠作为对照。通过测量血清肌酐、血尿素氮(BUN)、甘油三酯和尿蛋白水平来评估肾损伤。肾皮质匀浆用于估计炎症标志物肿瘤坏死因子-α(TNF-α)、氧化应激标志物丙二醛(MDA)以及两种抗氧化剂超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)的肾脏含量。此外,在第8周和第12周结束时摘取大鼠肾脏,检查组织学异常情况。

结果

接受ADR治疗的大鼠表现出FSGS的生化和组织学证据,表现为蛋白尿、血清肌酐、BUN和甘油三酯升高,肾脏TNF-α和MDA升高,以及节段性肾小球硬化。接受ADR-CUR治疗的大鼠所有这些变量均有显著改善。与姜黄素共同给药导致蛋白尿、血清肌酐、BUN和甘油三酯得到改善。抗氧化剂SOD和GSH的肾脏组织水平升高,TNF-α和MDA的水平降低,组织学显示节段性肾小球硬化程度减轻。姜黄素治疗显著对抗了与FSGS相关的肾损伤。

结论

我们的研究结果证实了姜黄素作为一种潜在治疗剂对预防FSGS进展具有肾脏保护作用,并表明其通过抑制氧化损伤和炎症以及促进抗氧化剂来减轻肾损伤。姜黄素改善了小鼠模型中ADR诱导的FSGS。它可能是治疗人类FSGS的一种有前景的化合物。需要更多的人体研究来进一步阐明其在FSGS中的作用。

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