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厄贝沙坦通过抑制 NF-κB 表达在急性肾损伤模型中恢复水通道蛋白-1 水平。

Irbesartan restored aquaporin-1 levels via inhibition of NF-kB expression in acute kidney injury model.

机构信息

Alanya Alaaddin Keykubat University, School of Medicine, Department of Anatomy, Alanya, Turkey.

Suleyman Demirel University, Faculty of Medicine, Department of Biochemistry, Isparta, Turkey.

出版信息

Nefrologia (Engl Ed). 2024 Jul-Aug;44(4):540-548. doi: 10.1016/j.nefroe.2023.11.003.

Abstract

INTRODUCTION

Acute kidney injury (AKI) is a serious pathology that progress with dysfunction of regulating blood pressure and fluid balance, concentrating urine due to decrement of aquaporin-1 (AQP) levels during the inflammation process. Irbesartan (IRN), angiotensin receptor blocker, is widely used in the treatment of hypertension, which also has anti-inflammatory, antioxidant and anti-apoptotic properties. The aim of this study is to investigate the protective effects of IRN in lipopolysaccharide (LPS)-induced kidney injury.

MATERIAL AND METHODS

Twenty-four rats divided into three groups as control, LPS and LPS+IRN group. After 6h of LPS administration, rats were sacrificed. Blood samples and half of the kidney tissues were collected for biochemical analysis and remaining tissues were taken for histopathological and immunohistochemical analysis.

RESULTS

In the LPS group, glomerular congestion and shrinkage, degeneration of distal tubules, mononuclear cell infiltration, cellular debris and intense proteinous accumulation in the tubules, increased expressions of Cas-3, nuclear factor kappa beta-p65 (NF-kB p65), levels of creatinin, TOS, OSI and decreased levels of TAS, AQP-1 were found significantly. IRN treatment reversed all these parameters. IRN's restorated AQP-1 levels by its anti-inflammatory, antioxidant and anti-apoptotic effects due to inhibiting NF-kB expression.

CONCLUSION

This study suggests that IRN can be used in conditions affecting the kidneys such as AKI. Further studies needed for detailed molecular investigation of IRN at different doses and durations.

摘要

介绍

急性肾损伤(AKI)是一种严重的病理学疾病,其特征是在炎症过程中由于水通道蛋白-1(AQP)水平的降低而导致血压和液体平衡调节功能障碍以及尿液浓缩。厄贝沙坦(IRN)是一种广泛用于治疗高血压的血管紧张素受体阻滞剂,它还具有抗炎、抗氧化和抗凋亡的特性。本研究旨在探讨 IRN 对脂多糖(LPS)诱导的肾损伤的保护作用。

材料和方法

将 24 只大鼠分为三组:对照组、LPS 组和 LPS+IRN 组。在给予 LPS 6 小时后,处死大鼠。采集血样和一半的肾脏组织进行生化分析,其余组织用于组织病理学和免疫组织化学分析。

结果

在 LPS 组中,发现肾小球充血和收缩、远端肾小管变性、单核细胞浸润、细胞碎片和管腔内强烈的蛋白质积聚、Cas-3、核因子 kappa beta-p65(NF-kB p65)表达增加,肌酐、TOS、OSI 水平升高,TAS、AQP-1 水平降低。IRN 治疗逆转了所有这些参数。IRN 通过抗炎、抗氧化和抗凋亡作用抑制 NF-kB 表达,从而恢复 AQP-1 水平。

结论

本研究表明,IRN 可用于影响肾脏的疾病,如 AKI。需要进一步研究不同剂量和时间的 IRN 的详细分子作用机制。

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