Abstract

Objectives

Inflammation as well as oxygen metabolite play important roles in renal injury during pathogenesis of rhabdomyolysis induced myoglobinuric acute renal failure (ARF). The aim of this study was to investigate the protective effects of donepezil on immune responses in rats with glycerol-induced ARF.

Methods

Sixty male rats were randomly divided into six groups, the rats were given normal saline (10 ml/kg, i.m.), glycerol (50%, 10 ml/kg, i.m.), glycerol plus dexamethasone (0.1 mg/kg, i.g.), and glycerol plus donepezil (1, 5 and 10 mg/kg, i.g.) respectively. After two weeks of glycerol injections, the kidney tissues and blood samples were harvested for future biochemical and pathology analysis. The levels of creatinine (Cr) and urea nitrogen (BUN) in plasma, the content of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activity, total nitric oxide synthase (TNOS), inducible nitric oxide synthase (iNOS), endothelial NO synthase (eNOS) were evaluated in renal tissues. In addition, interleukin-6 (IL-6), tumor necrosis factors-α (TNF-α) in renal tissues were also determined.

Results

Donepezil treatment protected rats from renal dysfunction in a dose-dependent manner and through the cholinergic anti-inflammatory pathway. Additionally, donepezil significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the IL-6, TNF-α, nitric oxide content and oxidative damage.

Conclusions

These data indicate that donepezil exerts a protective anti-inflammatory effect during ARF through the cholinergic pathway and Nitric oxide pathway. In addition, this study could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation and other injury.

中文翻译：

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多奈哌齐通过胆碱能抗炎和一氧化氮途径保护甘油诱导的急性肾衰竭

摘要

目标

在横纹肌溶解引起的肌红蛋白尿性急性肾衰竭（ARF）的发病机理中，炎症以及氧代谢产物在肾损伤中起重要作用。这项研究的目的是研究多奈哌齐对甘油诱导的ARF大鼠免疫反应的保护作用。

方法

60只雄性大鼠随机分为六组，分别给予生理盐水（10 ml / kg，im），甘油（50％，10 ml / kg，im），甘油加地塞米松（0.1 mg / kg，ig），和甘油加多奈哌齐（分别为1、5和10 mg / kg，ig）。注射甘油两周后，收集肾脏组织和血液样本以用于将来的生化和病理分析。血浆中的肌酐（Cr）和尿素氮（BUN），丙二醛（MDA）含量，谷胱甘肽（GSH）和超氧化物歧化酶（SOD）活性，总一氧化氮合酶（TNOS），诱导型一氧化氮合酶（ iNOS），内皮一氧化氮合酶（eNOS）在肾组织中进行了评估。另外，还测定了肾组织中的白细胞介素-6（IL-6），肿瘤坏死因子-α（TNF-α）。

结果

多奈哌齐治疗通过剂量依赖性方式和胆碱能抗炎途径保护大鼠免受肾功能不全的影响。此外，多奈哌齐显着减少了肾小管损害，防止了中性粒细胞浸润，并降低了IL-6，TNF-α，一氧化氮含量和氧化损伤的产生。

结论

这些数据表明多奈哌齐在ARF期间通过胆碱能途径和一氧化氮途径发挥保护性抗炎作用。此外，这项研究可能提供克服肾脏移植和其他损伤过程中手术胆碱能去神经作用的机会。