姜黄素对链脲佐菌素诱导的糖尿病肾病的肾保护作用：NOX2 和 Nrf2 信号的作用。

Renoprotective Effect of Thymoquinone against Streptozotocin-Induced Diabetic Nephropathy: Role of NOX2 and Nrf2 Signals.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, South Valley University, South Valley, Qena, Egypt.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt 71524.

出版信息

Curr Mol Pharmacol. 2023;16(8):905-914. doi: 10.2174/1874467216666230125150112.

DOI:10.2174/1874467216666230125150112

PMID:36698232

Abstract

OBJECTIVE

Diabetic nephropathy is an unavoidable complication of chronic uncontrolled diabetes mellitus. The pathogenesis of diabetic nephropathy is multifactorial, and the development of an effective therapy remains to be elucidated. The aim of the present study was to assess the role of NOX2 and Nrf2 in the protective mechanism of thymoquinone (THQ) against streptozotocin (STZ)-induced diabetic nephropathy.

METHODS

Rats were injected with STZ (55 mg/kg) to induce diabetes. The diabetic rats were orally treated with THQ (10 mg/kg/day) for eight weeks.

RESULTS

STZ-treated rats exhibit an elevation of serum creatinine, serum urea, and creatinine clearance. The renal abnormalities were associated with increased NADPH oxidase isoform, NOX2 protein expression, and activity, along with elevated malondialdehyde (MDA). In addition, the tumor necrotic factor-alpha (TNF-α) level and nitric oxide (NO) bioavailability, as well as the transforming growth factor-beta (TGF)-β, were markedly increased. On the other hand, the nuclear factor-E2-related factor (Nrf2) protein expression was significantly reduced in diabetic rats compared to the control. However, treatment with THQ significantly reversed these alterations with subsequent ameliorating renal dysfunction and pathological abnormalities.

CONCLUSION

The present study demonstrates that THQ could protect against STZ-induced diabetic nephropathy by modulating the Nrf2/NOX2 signaling pathway.

摘要

目的

糖尿病肾病是慢性未控制糖尿病的一种不可避免的并发症。糖尿病肾病的发病机制是多因素的，有效的治疗方法仍有待阐明。本研究旨在评估 Nrf2 在姜黄素（THQ）对链脲佐菌素（STZ）诱导的糖尿病肾病的保护机制中的作用。

方法

大鼠注射 STZ（55mg/kg）诱导糖尿病。糖尿病大鼠经口给予 THQ（10mg/kg/天）治疗 8 周。

结果

STZ 处理的大鼠表现出血清肌酐、血清尿素和肌酐清除率升高。肾脏异常与 NADPH 氧化酶同工型、NOX2 蛋白表达和活性的升高以及丙二醛（MDA）的升高有关。此外，肿瘤坏死因子-α（TNF-α）水平和一氧化氮（NO）的生物利用度以及转化生长因子-β（TGF-β）显著增加。另一方面，与对照组相比，糖尿病大鼠的核因子-E2 相关因子（Nrf2）蛋白表达明显降低。然而，THQ 治疗显著逆转了这些变化，随后改善了肾功能和病理异常。